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The timing and duration of the coldest period in the last glacial stage, often referred to as the last glacial maximum (LGM), has been observed to vary spatially and temporally. In Australia, this period is characterised by colder, and in some places more arid, climates than today. We applied Monte-Carlo change point analysis to all available continuous proxy records covering this period, primarily pollen records, from across Australia (n = 37) to assess this change. We find a significant change point occurred (within uncertainty) at 28.6 ± 2.8 ka in 25 records. We interpret this change as a shift to cooler climates, associated with a widespread decline in biological productivity. An additional change point occurred at 17.7 ± 2.2 ka in 24 records. We interpret this change as a shift towards warmer climates, associated with increased biological productivity. We broadly characterise the period between 28.6 (± 2.8) – 17.7 (± 2.2) ka as an extended period of maximum cooling, with low productivity vegetation that may have occurred as a combined response to reduced temperatures, lower moisture availability and atmospheric CO2. These results have implications for how the spatial and temporal coherence of climate change, in this case during the LGM, can be best interrogated and interpreted.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (sd 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (sd 3), post 305 (sd 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (sd 3), post 288 (sd 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (sd 0·9) to 16·6 (sd 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (sd 2·0), 14·1 (sd 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.
When a poorly conducting drop that is surrounded by a more conducting exterior fluid is subjected to an electric field, the drop can deform into an oblate shape at low field strengths. Such drops become unstable at high field strengths and display two types of dynamics, dimpling and equatorial streaming, the physics of which is currently not understood. If the drop is more viscous, dimples form and grow at the poles of the drop and eventually the discocyte-shaped drop breaks up to form a torus. If the exterior fluid is more viscous, the drop deforms into a lens and sheds rings from the equator that subsequently break into a number of smaller droplets. A theoretical explanation as to why dimple- and lens-shaped drops occur, and the mechanisms for the onset of these instabilities, are provided by determining steady-state solutions by simulation and inferring their stability from bifurcation analysis. For large drop viscosities, electric shear stress is shown to play a dominant role and to result in dimpling. For small drop viscosities, equatorial normal stresses (electric, hydrodynamic and capillary) become unbounded and lead to the lens shape.
Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.
EXPLORING THE INTERNAL DECISION-MAKING PROCESSES OF COLLEGIAL COURTS
In advance of the conference for which this chapter was written, Professor Wolfgang Ernst prepared a very thoughtful essay on ‘Designing Collegiate Courts‘ Decision Making Processes – The Fine-Mechanics of Judicial Majoritarianism‘, in which he offered his view of the core problem of collegiate courts:
’In all collegiate courts disagreement between judges must, at least to some degree, be overcome in order to see the pending case decided …. There is a great variety of approaches to what seems to be the core problem of collegiate courts: How to come to a decision in spite of judges‘ disagreement? Insofar as judicial majority-seeking takes place in a conference of judges, the competences and procedures of such conferences are pertinent issues ….
The method by which several judges‘ opinions are fused in deciding the case at hand, and also in shaping the law of the land, is a decisive moment in the exercise of judicial power.‘
Professor Ernst‘s essay reflects on some of the perceived differences between ‘Anglo-American judicial systems‘ and typical ‘continental/civilian judicial system[s]‘. He says that in Anglo-American judicial systems,
’the case at hand is decided by the majority of opinions, the order of the court being established by looking at the constituent individual judges‘ conclusions and end results. The unitary order of the court may be accompanied by multiple reasoning, each opinion developed independently by any judge who finds he must express his individual view of the case.‘
In contrast, Professor Ernst explains that in continental/civilian judicial systems,
‘decision making power [typically] lies with the conference of judges alone. Here, every judge – as a member of the conference – can just do his best to influence the collective decision. However, [the judge] cannot fall back on an individual decision, if he feels that reaching an agreement would unduly compromise his individual view of the case.‘
Poor post-prandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so the present study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised crossover design, fifteen adults (seven males, eight females; age, 22 (sd 3) years; BMI, 24·0 (sd 2·8) kg/m2; fasting blood glucose, 4·9 (sd 0·5) mmol/l) woke at 04.00 (sd 1) hours to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate/kg body mass, 2356 (sd 435) kJ), 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental AUC) to breakfast by 43·5 (sd 55·5) mmol × 120 min/l (P = 0·009, d = 0·94). Consistent with this effect, individual peak blood glucose concentrations were 0·6 (sd 1·0) mmol/l higher following breakfast when protein had been ingested (P = 0·049, d = 0·50). Immediately prior to breakfast, rates of lipid oxidation were 0·02 (sd 0·03) g/min higher (P = 0·045) in the protein condition, followed by an elevated post-prandial energy expenditure (0·38 (sd 0·50) kJ/min, P = 0·018). Post-prandial appetite and energy intake were similar between conditions. The present study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing post-prandial energy expenditure.
Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00–07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.
Introduction: The ways in which Emergency Medicine (EM) physicians interact with the medical literature has been transformed with the rise of Free Open Access Medical Education (FOAM). Although nearly all residents use FOAM resources, some criticize the lack of universal quality assurance. This problem is a particular risk for trainees who have many time constraints and incompletely developed critical appraisal skills. One potential safeguard is journal club, which is used by virtually all EM residency programs in North America to review new literature. However, EM resident perspectives have not been studied. Our research objective was to describe how residents perceive journal club to influence how they translate the medical literature into their clinical practice. Our research question was whether FOAM has influenced residents’ goals and perceived value of journal club. Methods: We developed a semi-structured interview script in conjunction with a methods expert and refined it via pilot testing. Following constructivist grounded theory, and using both purposive and theoretical sampling, we conducted a focus group (n = 7) and 18 individual interviews with EM residents at the 4 training sites of the University of British Columbia. In total, we analyzed 920 minutes of recorded audio. Two authors independently coded each transcript, with discrepancies reconciled by discussion and consensus. Constant comparative analysis was performed. We conducted return of findings through public presentations. Results: We found evidence that journal club works as a community of practice with a progression of roles from junior to senior residents. Participants described journal club as a safe venue to compare practice patterns and to gain insight into the practical wisdom of their peers and mentors. The social and academic activities present at journal club interacted positively to foster this environment. In asking residents about ways that journal club accelerates knowledge translation, we actually found that residents cite journal club as a quality check to prevent premature adoption of new research findings. Residents are hesitant to adopt new literature into their practice without positive validation, which can occur during journal club. Conclusion: Journal club functions as a community of practice that is valued by residents. Journal club is a primary way that new evidence can be validated before being put into practice, and may act as quality assurance in the era of FOAM.
Stability of a solitary wave disturbed by a submerged flat sill is investigated experimentally. For sills narrow compared with the solitary wave, the transmitted waves are found to be unaffected in waveform and amplitude. A wider sill disturbs the solitary wave resulting in the formation of a dispersive wavetrain following the transmitted wave. In some cases, the wave amplitude recovers, despite being perturbed, to the state of an unobstructed solitary-wave state at a certain distance beyond the sill. Wider sills cause wave breaking that occurs over the sill or, in some cases, after the wave passes through the sill. Details of waveform transformation leading toward the breaking and subsequent energy dissipation are discussed.
Research opportunities associated with the proliferation of the electronic health record (EHR), big data initiatives, and innovative approaches to trial design can present challenges for obtaining and documenting informed consent. Broad-scale informed consent (a term used herein to describe institutional models, rather than the Common Rule’s strict regulatory definition for “broad consent”) may facilitate the use of existing data and samples and speed the pace of research by minimizing barriers to consent. We explored the use of broad-scale informed consent within the Clinical Translational Science Award (CTSA) Program Network.
We surveyed CTSA Hubs concerning policies, practices, experiences, and needs within three domains of broad-scale informed consent: (1) participant recontact; (2) biospecimens; and (3) clinical data sharing.
Of 61 CTSA Hubs surveyed, 37 (61%) indicated ongoing work related to at least 1 domain of broad-scale informed consent; 18 Hubs (30%) reported work in all 3 domains. The EHR predominated as the implementation system across all three domains. Research and IT leadership and the Institutional Review Board were most commonly endorsed as institutional drivers, while systems/technical issues and impact on clinical workflow were the most commonly reported barriers.
While survey results indicate considerable variability in the implementation of broad-scale informed consent across the CTSA consortium, it is clear that all CTSA Hubs are actively considering policy and process related to these concepts. Next steps cluster within three areas: training and workforce development, streamlined policies and templates, and implementation strategies that facilitate integration into clinical workflow.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Regional to global high-resolution correlation and timing is critical when attempting to answer important geological questions, such as the greenhouse to icehouse transition that occurred during the Eocene–Oligocene boundary transition. Timing of these events on a global scale can only be answered using correlation among many sections, and multiple correlation proxies, including biostratigraphy, lithostratigraphy, geochemistry and geophysical methods. Here we present litho- and biostratigraphy for five successions located in the southeastern USA. To broaden the scope of correlation, we also employ carbon and oxygen stable isotope and magnetic susceptibility (χ) data to interpret these sections regionally, and correlate to the Global Boundary Stratotype Section and Point (GSSP) near Massignano in central Italy. Our results indicate that approaching the Eocene–Oligocene boundary, climate warmed slightly, but then δ18O data exhibit an abrupt c. +5 ‰ positive shift towards cooling that reached a maximum c. 1 m below the boundary at St Stephens Quarry, Alabama. This shift was accompanied by a c. −3 ‰ negative shift in δ13C interpreted to indicate environmental changes associated with the onset of the Eocene–Oligocene boundary planktonic foraminiferal extinction event. The observed cold pulse may be responsible for the final extinction of Hantkeninidae, used to define the beginning of the Rupelian Stage. Immediately preceding the boundary, Hantkeninidae species dropped significantly in abundance and size (pre-extinction dwarfing occurring before the final Eocene–Oligocene extinctions), and these changes may be the reason for inconsistencies in past Eocene–Oligocene boundary placement in the southeastern USA.