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The concentration of radiocarbon (14C) differs between ocean and atmosphere. Radiocarbon determinations from samples which obtained their 14C in the marine environment therefore need a marine-specific calibration curve and cannot be calibrated directly against the atmospheric-based IntCal20 curve. This paper presents Marine20, an update to the internationally agreed marine radiocarbon age calibration curve that provides a non-polar global-average marine record of radiocarbon from 0–55 cal kBP and serves as a baseline for regional oceanic variation. Marine20 is intended for calibration of marine radiocarbon samples from non-polar regions; it is not suitable for calibration in polar regions where variability in sea ice extent, ocean upwelling and air-sea gas exchange may have caused larger changes to concentrations of marine radiocarbon. The Marine20 curve is based upon 500 simulations with an ocean/atmosphere/biosphere box-model of the global carbon cycle that has been forced by posterior realizations of our Northern Hemispheric atmospheric IntCal20 14C curve and reconstructed changes in CO2 obtained from ice core data. These forcings enable us to incorporate carbon cycle dynamics and temporal changes in the atmospheric 14C level. The box-model simulations of the global-average marine radiocarbon reservoir age are similar to those of a more complex three-dimensional ocean general circulation model. However, simplicity and speed of the box model allow us to use a Monte Carlo approach to rigorously propagate the uncertainty in both the historic concentration of atmospheric 14C and other key parameters of the carbon cycle through to our final Marine20 calibration curve. This robust propagation of uncertainty is fundamental to providing reliable precision for the radiocarbon age calibration of marine based samples. We make a first step towards deconvolving the contributions of different processes to the total uncertainty; discuss the main differences of Marine20 from the previous age calibration curve Marine13; and identify the limitations of our approach together with key areas for further work. The updated values for ΔR, the regional marine radiocarbon reservoir age corrections required to calibrate against Marine20, can be found at the data base http://calib.org/marine/.
Preferential removal of W relative to other trace elements from zoned, W–Sn–U–Pb-bearing hematite coupled with disturbance of U–Pb isotope systematics is attributed to pseudomorphic replacement via coupled dissolution reprecipitation reaction (CDRR). This hematite has been studied down to the nanoscale to understand the mechanisms leading to compositional and U/Pb isotope heterogeneity at the grain scale. High-Angle Annular Dark Field Scanning Transmission Electron Microscopy (HAADF STEM) imaging of foils extracted in situ from three locations across the W-rich to W-depleted domains show lattice-scale defects and crystal structure modifications adjacent to twin planes. Secondary sets of twins and associated splays are common, but wider (up to ~100 nm) inclusion trails occur only at the boundary between the W-rich and W-depleted domains. STEM energy-dispersive X-ray mapping reveals W- and Pb-enrichment along 2–3 nm-wide features defining the twin planes; W-bearing nanoparticles occur along the splays. Tungsten and Pb are both present, albeit at low concentrations, within Na–K–Cl-bearing inclusions along the trails. HAADF STEM imaging of hematite reveals modifications relative to ideal crystal structure. A two-fold hematite superstructure (a = b = c = 10.85 Å; α = β = γ = 55.28°) involving oxygen vacancies was constructed and assessed by STEM simulations with a good match to data. This model can account for significant W release during interaction with fluids percolating through twin planes and secondary structures as CDRR progresses from the zoned domain, otherwise apparently undisturbed at the micrometre scale. Lead remobilisation is confirmed here at the nanoscale and is responsible for a disturbance of U/Pb ratios in hematite affected by CDRR. Twin planes can provide pathways for fluid percolation and metal entrapment during post-crystallisation overprinting. The presence of complex twinning can therefore predict potential disturbances of isotope systems in hematite that will affect its performance as a robust geochronometer.
Prognosis and disposition among older emergency department (ED) patients with suspected infection remains challenging. Frailty is increasingly recognized as a predictor of poor prognosis among critically ill patients; however, its association with clinical outcomes among older ED patients with suspected infection is unknown.
We conducted a multicenter prospective cohort study at two tertiary care EDs. We included older ED patients (≥75 years) with suspected infection. Frailty at baseline (before index illness) was explicitly measured for all patients by the treating physicians using the Clinical Frailty Scale (CFS). We defined frailty as a CFS 5–8. The primary outcome was 30-day mortality. We used multivariable logistic regression to adjust for known confounders. We also compared the prognostic accuracy of frailty with the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) criteria.
We enrolled 203 patients, of whom 117 (57.6%) were frail. Frail patients were more likely to develop septic shock (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.08–2.51) and more likely to die within 30 days of ED presentation (aOR 2.05; 95% CI, 1.02–5.24). Sensitivity for mortality was highest among the CFS (73.1%; 95% CI, 52.2–88.4), compared with SIRS ≥ 2 (65.4%; 95% CI, 44.3–82.8) or qSOFA ≥ 2 (38.4; 95% CI, 20.2–59.4).
Frailty is a highly prevalent prognostic factor that can be used to risk-stratify older ED patients with suspected infection. ED clinicians should consider screening for frailty to optimize disposition in this population.
Introduction: A critical component for successful implementation of any innovation is an organization's readiness for change. Competence by Design (CBD) is the Royal College's major change initiative to reform the training of medical specialists in Canada. The purpose of this study was to measure readiness to implement CBD among the 2019 launch disciplines. Methods: An online survey was distributed to program directors of the 2019 CBD launch disciplines one month prior to implementation. Questions were developed based on the R = MC2 framework for organizational readiness. They addressed program motivation to implement CBD, general capacity for change, and innovation-specific capacity. Questions related to motivation and general capacity were scored using a 5-point scale of agreement. Innovation-specific capacity was measured by asking participants whether they had completed 33 key pre-implementation tasks (yes/no) in preparation for CBD. Bivariate correlations were conducted to examine the relationship between motivation, general capacity and innovation specific capacity. Results: Survey response rate was 42% (n = 79). A positive correlation was found between all three domains of readiness (motivation and general capacity, r = 0.73, p < 0.01; motivation and innovation specific capacity, r = 0.52, p < 0.01; general capacity and innovation specific capacity, r = 0.47, p < 0.01). Most respondents agreed that successful launch of CBD was a priority (74%). Fewer felt that CBD was a move in the right direction (58%) and that implementation was a manageable change (53%). While most programs indicated that their leadership (94%) and faculty and residents (87%) were supportive of change, 42% did not have experience implementing large-scale innovation and 43% indicated concerns about adequate support staff. Programs had completed an average of 72% of pre-implementation tasks. No difference was found between disciplines (p = 0.11). Activities related to curriculum mapping, competence committees and programmatic assessment had been completed by >90% of programs, while <50% of programs had engaged off-service rotations. Conclusion: Measuring readiness for change aids in the identification of factors that promote or inhibit successful implementation. These results highlight several areas where programs struggle in preparation for CBD launch. Emergency medicine training programs can use this data to target additional implementation support and ongoing faculty development initiatives.
Introduction: Prognostication and disposition among older Emergency Department (ED) patients with suspected infection remains challenging. Frailty is increasingly recognized as a predictor of poor prognosis among critically ill patients, however its association with clinical outcomes among older ED patients with suspected infection is unknown. Methods: We conducted a multicentre prospective cohort study at two tertiary care EDs. We included older ED patients (≥ 75 years) presenting with suspected infection. Frailty at baseline (prior to index illness) was explicitly measured for all patients by the treating physicians using the Clinical Frailty Scale (CFS). We defined frailty as a CFS 5-8. The primary outcome was 30-day mortality. We used multivariable logistic regression to adjust for known confounders. We also compared the prognostic accuracy of frailty against the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) criteria. Results: We enrolled 203 patients, of whom 117 (57.6%) were frail. Frail patients were more likely to develop septic shock (adjusted odds ratio [aOR]: 1.83, 95% confidence interval [CI]: 1.08-2.51) and more likely to die within 30 days of ED presentation (aOR 2.05, 95% CI: 1.02-5.24). Sensitivity for mortality was highest among the CFS (73.1%, 95% CI: 52.2-88.4), as compared to SIRS ≥ 2 (65.4%, 95% CI: 44.3-82.8) or qSOFA ≥ 2 (38.4, 95% CI: 20.2-59.4). Conclusion: Frailty is a highly prevalent prognostic factor that can be used to risk-stratify older ED patients with suspected infection. ED clinicians should consider screening for frailty in order to optimize disposition in this population.
The volume of evidence from scientific research and wider observation is greater than ever before, but much is inconsistent and scattered in fragments over increasingly diverse sources, making it hard for decision-makers to find, access and interpret all the relevant information on a particular topic, resolve seemingly contradictory results or simply identify where there is a lack of evidence. Evidence synthesis is the process of searching for and summarising a body of research on a specific topic in order to inform decisions, but is often poorly conducted and susceptible to bias. In response to these problems, more rigorous methodologies have been developed and subsequently made available to the conservation and environmental management community by the Collaboration for Environmental Evidence. We explain when and why these methods are appropriate, and how evidence can be synthesised, shared, used as a public good and benefit wider society. We discuss new developments with potential to address barriers to evidence synthesis and communication and how these practices might be mainstreamed in the process of decision-making in conservation.
The front-line nature of mental health crisis services and the complex and acute presentations of their clients, require rapid decisions in response to medication requests. Prescribing is conducted by a combination of non-medical prescribers, advanced practitioners and medical professionals, with individual variation in prescribing habits and trends. This leads to an impact on the prescribing budget with spiraling costs evident.
We undertook an audit of the prescriptions issued for emergency medications over 6 months. We incorporated audit standards, from NICE guidelines for prescribing of psychotropic medications and local trust prescribing advice. We audited data to examine whether cost of medication had been considered, in the context of the efficacy and safety of medications.
Of 138 prescriptions issued, 72 (52%) were prescribed by advanced practitioners, 7 by non-medical prescribers (5%) and the remainder by doctors (43%). 213 items were prescribed costing £2828 during this period. We demonstrated, by introducing smarter prescribing methods, a reduction in the number of prescription items by 27.7% (59 items), resulting in a financial efficiency of 94.6% (£2677). We recommended implementing an acute care formulary acting as a guide to smarter prescribing.
The guide includes recommending generic versions of medications instead of trade brands, asking primary care to initiate medications, reducing quantities of drugs prescribed, increased accountability for prescribing decisions and stopping use of expensive psychotropics, where cheaper alternatives with similar efficacy and side effect profile are available. To assess impact, we would reaudit in 6 months, before consideration towards adopting the policy trustwide.
We investigate how early exposure to parental externalizing behaviors (EB) may contribute to development of alcohol use disorders (AUD) in young adulthood, testing a developmental cascade model focused on competencies in three domains (academic, conduct, and work) in adolescence and emerging adulthood, and examining whether high parental education can buffer negative effects of parental EB and other early risk factors. We use data from 451,054 Swedish-born men included in the national conscript register. Structural equation models showed parental EB was associated with academic and behavioral problems during adolescence, as well as with lower resilience, more criminal behavior, and reduced social integration during emerging adulthood. These pathways led to elevated rates of AUD in emerging and young adulthood. Multiple groups analysis showed most of the indirect pathways from parental EB to AUD were present but buffered by higher parental education, suggesting early life experiences and competencies matter more for young men from lower socioeconomic status (SES) families than from higher SES families. Developmental competencies in school, conduct, and work are important precursors to the development of AUD by young adulthood that are predicted by parental EB. Occupational success may be an overlooked source of resilience for young men from low-SES families.
Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.
Ground-penetrating radar data acquired in the 2016/17 austral summer on Sørsdal Glacier, East Antarctica, provide evidence for meltwater lenses within porous surface ice that are conceptually similar to firn aquifers observed on the Greenland Ice Sheet and the Arctic and Alpine glaciers. These englacial water bodies are associated with a dry relict surface basin and consistent with perennial drainage into an interconnected englacial drainage system, which may explain a large englacial outburst flood observed in satellite imagery in the early 2016/17 melt season. Our observations indicate the rarely-documented presence of an englacial hydrological system in Antarctica, with implications for the storage and routing of surface meltwater. Future work should ascertain the spatial prevalence of such systems around the Antarctic coastline, and identify the degree of surface runoff redistribution and storage in the near surface, to quantify their impact on surface mass balance.
This article, the first detailed scholarly assessment of northern responses to the death of former Confederate President Jefferson Davis in December 1889, contributes to ongoing academic debates over the troubled process of sectional reconciliation after the Civil War. Southern whites used their leader's funeral obsequies to assert not only their affection for the deceased but also their devotion to the Lost Cause that he had championed and embodied. Based on an analysis of northern newspapers and mass-circulation magazines in the two weeks after Davis's death, the essay demonstrates that many northerners, principally Republican politicians and editors, Union veterans, and African Americans, were outraged by southerners’ flagrant willingness to laud a man whom they regarded as the arch-traitor and that they remained opposed to reconciliation on southern terms. However, despite continuing concerns about public displays of affection for the Confederacy evident at the time of Davis's reinterment in Richmond in May 1893, northern opposition to the Lost Cause waned rapidly in the last decade of the nineteenth century. Full-blown sectional reconciliation occurred after the Republicans gave up on their efforts to enforce black voting rights in the South and President William McKinley's imperialist foreign policy necessitated, and to some degree garnered, support from southern whites. The death of Jefferson Davis, therefore, can be seen as an important event in the difficult transition from a heavily sectionalized postwar polity to a North-South rapprochement based heavily on political pragmatism, sentiment, nationalism, and white supremacism.
Tree-ring reconstructions of temperature often target trees at altitudinal or latitudinal tree line where annual growth is broadly expected to be limited by and respond to temperature variability. Based on this principal, regions with sparse tree line would seem to be restricted in their potential to reconstruct past temperatures. In the northeastern United States, there are only two published temperature reconstructions. Previous work in the region reconstructing moisture availability, however, has shown that using a greater diversity of species can improve reconstruction model skill. Here, we use a network of 228 tree-ring records composed of 29 species to test the hypothesis that an increase in species diversity among the pool of predictors improves reconstructions of past temperatures. Chamaecyparis thyoides alone explained 31% of the variability in observed cool-season minimum temperatures, but a multispecies model increased the explained variance to 44%. Liriodendron tulipifera, a species not previously used for temperature reconstructions, explained a similar amount of variance as Chamaecyparis thyoides (12.9% and 20.8%, respectively). Increasing the species diversity of tree proxies has the potential for improving reconstruction of paleotemperatures in regions lacking latitudinal or elevational tree lines provided that long-lived hardwood records can be located.
Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings – regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005–2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.
Expression of estrus (EST) near the time of fixed-time artificial insemination (FTAI) increases pregnancy success in beef females. This outcome has been associated with improved pregnancy establishment and maintenance, although research is still warranted to validate this theory. Hence, this experiment compared ovarian, uterine and conceptus factors associated with pregnancy establishment in Bos indicus beef cows according to estrous expression during a FTAI protocol. One hundred lactating multiparous Nelore cows received a 2 mg injection of estradiol benzoate and an intravaginal progesterone (P4) releasing device on day −11, a 12.5 mg injection of prostaglandin F2α on day −4, P4 device removal in addition to 0.6 mg injection of estradiol cypionate and 300 IU injection of equine chorionic gonadotropin on day −2, and FTAI on day 0. An estrous detection patch was attached to the tailhead of each cow on day −2, and estrous expression was defined as removal of >50% of the rub-off coating from the patch at FTAI. Overall, 39 cows expressed EST, 55 did not express EST (NOEST), and six cows lost their patch and were discarded from the experiment. Ovarian ultrasonography was performed at FTAI, and on days 7 and 15 of the experiment. Blood samples were also collected on days 7 and 15. Only cows without a corpus luteum (CL) on day 0, and with a CL on days 7 and 15 remained in the experiment (EST, n=36; NOEST, n=48). On day 15, cows were randomly selected within each group (EST, n=29; NOEST, n=30) for conceptus collection via transcervical flushing, followed by endometrial biopsy in the uterine horn ipsilateral to the CL. Within cows not assigned to conceptus collection, blood samples were collected for whole blood RNA extraction (day 20) and pregnancy status was verified by transrectal ultrasonography (day 30). Diameter of dominant follicle on day 0 and plasma P4 concentrations on day 7 were greater (P⩽0.02) in EST v. NOEST cows. Conceptus length and messenger RNA (mRNA) expression of prostaglandin E synthase and interferon-tau were greater (P⩽0.04) in EST v. NOEST cows. Moreover, EST cows diagnosed as pregnant on day 30 had greater (P<0.01) blood mRNA expression of myxovirus resistance 2 on day 20 compared with NOEST. In summary, estrous expression near the time of FTAI enhanced pregnancy establishment factors in B. indicus cows, including conceptus development and mRNA expression of interferon-tau.
Patulous Eustachian tube is a benign but notoriously difficult condition to treat successfully. Symptoms include autophony of voice and breathing, and aural fullness.
This paper presents a series of 8 patients (12 ears) for whom a novel computed tomography guided injection of silicone elastomer suspension implant (Vox) was used to treat patulous Eustachian tube. This is the largest and only series in the current literature using this technique.
The combined complete and partial symptom resolution rate was 91 per cent. Complications related to the procedure are described. The pros and cons of this novel approach are also discussed in relation to traditional endoscopic transnasal techniques.
Computed tomography guided injection of Vox for the treatment of patulous Eustachian tube is suggested to be a feasible alternative to endoscopic transnasal approaches, particularly for refractory cases.
Instrumental variable (IV) methods are widely used to address endogeneity concerns. Yet, a specific kind of endogeneity – spatial interdependence – is regularly ignored. We show that ignoring spatial interdependence in the outcome results in asymptotically biased estimates even when instruments are randomly assigned. The extent of this bias increases when the instrument is also spatially clustered, as is the case for many widely used instruments: rainfall, natural disasters, economic shocks, and regionally- or globally-weighted averages. Because the biases due to spatial interdependence and predictor endogeneity can offset, addressing only one can increase the bias relative to ordinary least squares. We demonstrate the extent of these biases both analytically and via Monte Carlo simulation. Finally, we discuss a general estimation strategy – S-2SLS – that accounts for both outcome interdependence and predictor endogeneity, thereby recovering consistent estimates of predictor effects.