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Igor Stravinsky is one of a small number of early modernist composers whose music epitomises the stylistic crisis of twentieth-century music, from the Russian nationalist heritage of the early works, the neo-classical works which anticipate the stylistic diversity of the contemporary musical scene in the early twenty-first century and the integration of serial techniques during his final period. With entries written by more than fifty international contributors from Russian, European and American traditions, The Cambridge Stravinsky Encyclopedia presents multiple perspectives on the life, works, writings and aesthetic relationships of this multi-faceted creative artist. This important resource explores Stravinsky's relationships with virtually all the major artistic figures of his time, painters, dramatists, choreographers and producers as well musicians and brings together fresh insights into to the life and work of one of the twentieth century's greatest composers.
Debate about the nature of climate and the magnitude of ecological change across Australia during the last glacial maximum (LGM; 26.5–19 ka) persists despite considerable research into the late Pleistocene. This is partly due to a lack of detailed paleoenvironmental records and reliable chronological frameworks. Geochemical and geochronological analyses of a 60 ka sedimentary record from Brown Lake, subtropical Queensland, are presented and considered in the context of climate-controlled environmental change. Optically stimulated luminescence dating of dune crests adjacent to prominent wetlands across North Stradbroke Island (Minjerribah) returned a mean age of 119.9 ± 10.6 ka; indicating relative dune stability soon after formation in Marine Isotope Stage 5. Synthesis of wetland sediment geochemistry across the island was used to identify dust accumulation and applied as an aridification proxy over the last glacial-interglacial cycle. A positive trend of dust deposition from ca. 50 ka was found with highest influx occurring leading into the LGM. Complexities of comparing sedimentary records and the need for robust age models are highlighted with local variation influencing the accumulation of exogenic material. An inter-site comparison suggests enhanced moisture stress regionally during the last glaciation and throughout the LGM, returning to a more positive moisture balance ca. 8 ka.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
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Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
Intentional facial disfigurement is documented in archaeological contexts around the world. Here, the authors present the first archaeological evidence for intentional facial mutilation from Anglo-Saxon England—comprising the removal of the nose, upper lip and possible scalping—inflicted upon a young adult female. The injuries are consistent with documented punishments for female offenders. Although such mutilations do not appear in the written record until the tenth century AD, the instance reported here suggests that the practice may have emerged a century earlier. This case is examined in the context of a wider consideration of the motivations and significance of facial disfigurement in past societies.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization has been a well-established risk for developing MRSA pneumonia. In previous studies, the MRSA nasal screening test has shown an excellent negative predictive value (NPV) for MRSA pneumonia in patients without exclusion criteria such as mechanical ventilation, hemodynamic instability, cavitary lesions, and underlying pulmonary disease. MRSA nasal screening can be used as a stewardship tool to de-escalate broad antibiotic coverage, such as vancomycin. Objective: The purpose of this study was to determine whether implementation of a MRSA nasal screening questionnaire improves de-escalation of vancomycin for patients with pneumonia. Methods: A retrospective review was performed on 250 patients from October 2018 to January 2019 who received MRSA nasal screening due to their prescriber choosing only “respiratory” on the vancomycin dosing consult form. Data obtained included demographics and clinical outcomes. Statistical analyses were performed, and P < .05 was considered significant. Results: Of the 250 patients screened, only 19 patients (8%) were positive for MRSA. Moreover, 40% of patients met exclusion criteria. In 149 patients without exclusion criteria, the MRSA nasal swab had a 98% NPV. Although not statistically significant, vancomycin days of therapy (DOT) based on MRSA nasal swab result was 1 day shorter in those with negative swabs (3.49 days negative vs 4.58 days positive; P = .22). Vancomycin DOT was significantly reduced in pneumonia patients without exclusion criteria (3.17 days “no” vs 4.17 days “yes”; P = .037). Conclusions: The implementation of an electronic MRSA nasal screening questionnaire resulted in reduced vancomycin DOT in pneumonia patients at UAB Hospital. The MRSA nasal swab is an effective screening tool for antibiotic de-escalation based on its 98% NPV for MRSA pneumonia if utilized in the correct patient population.
Disclosures: Rachael Anne Lee reports a speaker honoraria from Prime Education, LLC.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
OBJECTIVES/GOALS: African-Americans have a 3-fold higher risk of end-stage kidney disease (ESKD) compared to Whites due in part to APOL1 risk alleles. Whether resistant hypertension (RH) magnifies the risk of ESKD among African Americans beyond APOL1 is not known. We examined the interaction between RH and race on ESKD risk and the independent effect of RH beyond APOL1. METHODS/STUDY POPULATION: We designed a retrospective cohort of 240,038 veterans with HTN, enrolled in the Million Veteran Program with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2. The primary exposure was incident RH (time-varying). The primary outcome was incident ESKD during a 13.5 year follow up: 2004-2017. Secondary outcomes were myocardial infarction (MI), stroke, and death. Incident RH was defined as failure to achieve outpatient blood pressure (BP) <140/90 mmHg with 3 antihypertensive drugs, including a thiazide, or use of 4 or more drugs. Poisson models were used to estimate incidence rates and test additive interaction with race and APOL1 genotype. Multivariable Cox models (with Fine-Gray competing-risks models as sensitivity analyses) were used to examine independent effects. RESULTS/ANTICIPATED RESULTS: The cohort comprised 235,046 veterans; median age was 60 years; 21% were African-American and 6% were women, with 23,010 incident RH cases observed over a median follow-up time of 10.2 years [interquartile range, 5.6-12.6]. Patients with RH had higher incidence rates [per 1000 person-years] of ESKD (4.5 vs. 1.3), myocardial infarction (6.5 vs. 3.0), stroke (16.4 vs. 7.6) and death (12.0 vs. 6.9) than non-resistant hypertension (NRH). African-Americans with RH had a 2.6-fold higher risk of ESKD compared to African-Americans with NRH; 3-fold the risk of Whites with RH, and 9.6-fold the risk of Whites with NRH [p-interaction<.001]. Among African-Americans, RH was associated with a 2.2-fold (95%CI, 1.86-2.58) higher risk of incident ESKD in models adjusted for APOL1 genotype and in the subset of African-Americans with no APOL1 risk alleles, RH was associated with an adjusted 2.75-fold (95% CI: 2.00-3.50) higher risk of incident ESKD. DISCUSSION/SIGNIFICANCE OF IMPACT: RH was independently associated with a higher risk of ESKD and cardiovascular outcomes, especially among African-Americans. This elevated risk is independent of APOL1 genotype. Interventions that achieve BP targets among patients with RH could curtail the incidence of ESKD and cardiovascular outcomes in this high-risk population. CONFLICT OF INTEREST DESCRIPTION: None.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence from randomized controlled trials have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan soluble fiber. However, oats contain an array of phenolic acids, including ferulic acid and also structurally related avenanthramides, which may also contribute to the cardiovascular health benefits of oat intake. We investigated whether 4 weeks, daily consumption of oat phenolics leads to improvement in markers of CVD risk men and women.In a 3 arm crossover single-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (-containing 48.9 mg of phenolic acids and 19.2 mg of avenanthramides); 2) oatbran concentrate + rice porridge/wheat cracker intervention (-containing 38.4 mg of phenolic acids and 0.5 mg of avenanthramides) or 3) rice porridge/wheat cracker intervention (containing 13.8 mg of phenolic acids). All treatments were matched in soluble fiber (4.8g) and energy (500kcal). The primary endpoint was FMD and other cardiovascular endpoints were blood pressure, LDI, LDL/HDL cholesterol, platelets and endothelial cell-derived extracellular vesicles (EVs). All measures were taken at baseline and after three, 4 week long intervention periods and two washout periods.Our data indicates an increase by 1.09 % ± 0.41 %(Mean ± SEM) in FMD response following high phenolic oat intake with a significant difference (P = 0.007) between baseline and post-intervention. Consumption of high phenolic oats also led to a significant improvement in 24-hour SBP, day time SBP and night time SBP (P < 0.01, P < 0.01 and P < 0.05) and day time and night time DBP (p < 0.05). There was also a significant decrease with total and LDL cholesterol after the consumption of moderate and high phenolic oat interventions (P < 0.05) and a small improvement in LDI (both Ach and SNP) but not significant. The number of resting endothelial EVs were also found to be increasing after the consumption of high phenolic oats.The findings of this study may provide evidence about the role of oat phenolic acids and avenanthramides in cardiovascular health and contribute to more effective public health advice about the consumption of oats and healthy cardiovascular aging.
Internet of Things (IoT) devices such as connected sensors are increasingly being used in the public sector, often deployed and collecting data in public spaces. A theme commonly seen in the rhetoric surrounding public space IoT initiatives is empowerment, and these deployments are broadly perceived as beneficial by policy makers. However, such technology presents new governance challenges. It is important to ask who is empowered and who benefits, and we must ensure that such technological interventions follow democratic principles and are trusted by citizens. In this paper, we investigate how risk, transparency, and data governance require careful consideration in this domain, describing work which investigates how these combine to form components of trusted IoT ecosystems. This includes an overview of the landscape of public space IoT deployments, consideration of how they may often be subsumed in idealized smart city focused rhetoric, and discussion of how methodologies such as design fiction in community settings can uncover potential risks and concerns. Our findings suggest that agency, value and intent associated with IoT systems are key components that must be made transparent, particularly when multiple actors and stakeholders are involved. We suggest that good governance requires consideration of these systems in their entirety, throughout the full planning, implementation, and evaluation process, and in consultation with multiple stakeholders who are impacted, including the public. To achieve this effectively, we argue for transparency at the device and system level, which may require legislative change.
Disappointed by a series of failures on the part of kings to win back the Holy Land and burdened with a host of other responsibilities at the outset of his pontificate, Pope Innocent III in 1198 turned to another form of crusade management, one which employed the pastoral concerns for ecclesiastical and devotional reform developed at the new schools of Paris. That reform movement consisted of articulate papal letters regularly recorded in registers, trusted ecclesiastical administrators, talented papal legates, and inspired charismatic preachers. He also set about creating a home front for the crusade, one that made it the centre of a new pastoral reform mission that included every Christian, whether an actual crusader or not. This new home front was to be managed by ecclesiastical provinces and their cities and nobles, assisted by papal legates and reform and crusade preachers, and offering new and extensive spiritual privileges. This is the context and the outcome of the tournament at Ecry-sur-Aisne in November, 1198, the assembling of an army by the counts of Champagne/Brie, Blois, and Flanders/Hainaut and their novel financial arrangements with the Venetians. With characteristic attention to detail, Innocent also issued instructions for crusaders who failed to appear. Although no single source includes all of these decisions and Innocent's sustained attention, there is little doubt that Innocent III paid close attention to the crusade from the very beginning of his pontificate.
Keywords: Fourth Crusade, moral reform, Innocent III, papal legates, preachers, privileges, ecclesiastical provinces, plena potestas, pro peccatis exigentibus
In his experience of crusade both before and after his election and consecration in January and February 1198, Innocent III brought a new purpose to the idea of a military expedition to the Holy Land. That purpose was to link the crusade with a programme of moral reform that extended throughout twelfth-century Christendom and incorporated all Christians in quite original and inventive ways. That is, as James Powell, Brenda Bolton, Jessalynn Bird, Christoph Maier, and a number of other scholars have also pointed out, under Innocent and his successors the crusade took on a new identity, as an organizing pastoral vehicle for universal participation in Christian moral reform, thereby greatly augmenting the economy of salvation. To rethink the theology of crusade, however, was one thing; to inspire, organize, and launch a crusade of the new type was quite another.
C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.
To explore CRP in MDD and its phenotypic associations.
We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.
Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.
CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.
Declaration of interest
S.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.