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To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
made over a 288-MHz band centred at 887.5 MHz.
This work investigated the photophysical pathways for light absorption, charge generation, and charge separation in donor–acceptor nanoparticle blends of poly(3-hexylthiophene) and indene-C60-bisadduct. Optical modeling combined with steady-state and time-resolved optoelectronic characterization revealed that the nanoparticle blends experience a photocurrent limited to 60% of a bulk solution mixture. This discrepancy resulted from imperfect free charge generation inside the nanoparticles. High-resolution transmission electron microscopy and chemically resolved X-ray mapping showed that enhanced miscibility of materials did improve the donor–acceptor blending at the center of the nanoparticles; however, a residual shell of almost pure donor still restricted energy generation from these nanoparticles.
Across the globe, there has been a marked increase in longevity, but significant inequalities remain. These are exacerbated by inadequate access to proper nutrition and health care services and to reliable information to make the decisions related to nutrition and health care. Many in economically developing as well as developed societies are plagued with the double-burden of energy excess and undernutrition. This has resulted in mental and physical deterioration, increased non-communicable disease rates, lost productivity, increased medical costs and reduced quality of life. While adequate nutrition is fundamental to good health at all stages of the life course, the impact of diet on prolonging good quality of life during ageing remains unclear. For progress to continue, there is need for new and/or innovative approaches to promoting health as individuals age, as well as qualitative and quantitative biomarkers and other accepted tools that can measure improvements in physiological integrity throughout life. A framework for progress has been proposed by the World Health Organization in their Global Strategy and Action Plan on Ageing and Health. Here, we focused on the impact of nutrition within this framework, which takes a broad, person-centred emphasis on healthy ageing, stressing the need to better understand each individual's intrinsic capacity, their functional abilities at various life stages, and the impact of their mental, and physical health, as well as the environments they inhabit.
Around two-thirds of patients with auditory hallucinations experience derogatory and threatening voices (DTVs). Understandably, when these voices are believed then common consequences can be depression, anxiety and suicidal ideation. There is a need for treatment targeted at promoting distance from such voice content. The first step in this treatment development is to understand why patients listen to and believe voices that are appraised as malevolent.
To learn from patients their reasons for listening to and believing DTVs.
Theoretical sampling was used to recruit 15 participants with non-affective psychosis from NHS services who heard daily DTVs. Data were obtained by semi-structured interviews and analysed using grounded theory.
Six higher-order categories for why patients listen and/or believe voices were theorised. These were: (i) to understand the voices (e.g. what is their motive?); (ii) to be alert to the threat (e.g. prepared for what might happen); (iii) a normal instinct to rely on sensory information; (iv) the voices can be of people they know; (v) the DTVs use strategies (e.g. repetition) to capture attention; and (vi) patients feel so worn down it is hard to resist the voice experience (e.g. too mentally defeated to dismiss comments). In total, 21 reasons were identified, with all participants endorsing multiple reasons.
The study generated a wide range of reasons why patients listen to and believe DTVs. Awareness of these reasons can help clinicians understand the patient experience and also identify targets in psychological intervention.
This essay returns to the early nineteenth-century prehistory of ecology to argue that the anthropocentrism of Victorian social novels should be understood as a deliberate, pragmatic response to the ethical dilemmas of ecological entanglement—dilemmas visible by the late eighteenth century. Interspecies entanglement and its discontents provided the cornerstone of Malthus's infamous arguments about overpopulation in the Essay on the Principle of Population (1798). Inspired by Malthus's proto-ecological vision of endless interconnection, Harriet Martineau adopted it as the plot structure of her Illustrations of Political Economy (1832–34), some of the earliest and most influential examples of industrial fiction. Later social novelists borrowed Martineau's narrative technique of disclosing community by tracing material interdependence, but they excluded relations that crossed the species barrier. Those exclusions arose not from arrogance or ignorance of humanity's dependence on other species but from the decision to bracket often unanswerable questions arising from interspecies collectivity to foreground the practical importance of attending to the urgent needs of human beings.
The spread of invasive, non-native species is a key threat to biodiversity. Parasites can play a significant role by influencing their invasive host's survival or behaviour, which can subsequently alter invasion dynamics. The North American signal crayfish (Pacifastacus leniusculus) is a known carrier of Aphanomyces astaci, an oomycete pathogen that is the causative agent of crayfish plague and fatal to European crayfish species, whereas North American species are considered to be largely resistant. There is some evidence, however, that North American species, can also succumb to crayfish plague, though how A. astaci affects such ‘reservoir hosts’ is rarely considered. Here, we tested the impact of A. astaci infection on signal crayfish, by assessing juvenile survival and adult behaviour following exposure to A. astaci zoospores. Juvenile signal crayfish suffered high mortality 4-weeks post-hatching, but not as older juveniles. Furthermore, adult signal crayfish with high-infection levels displayed altered behaviours, being less likely to leave the water, explore terrestrial areas and exhibit escape responses. Overall, we reveal that A. astaci infection affects signal crayfish to a much greater extent than previously considered, which may not only have direct consequences for invasions, but could substantially affect commercially harvested signal crayfish stocks worldwide.
Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
Insomnia treatment using an internet-based cognitive–behavioural therapy
for insomnia (CBT-I) program reduces depression symptoms, anxiety
symptoms and suicidal ideation. However, the speed, longevity and
consistency of these effects are unknown.
To test the following: whether the efficacy of online CBT-I was sustained
over 18 months; how rapidly the effects of CBT-I emerged; evidence for
distinct trajectories of change in depressive symptoms; and predictors of
A randomised controlled trial compared the 6-week Sleep Healthy Using the
Internet (SHUTi) CBT-I program to an attention control program. Adults
(N=1149) with clinical insomnia and subclinical
depression symptoms were recruited online from the Australian
Depression, anxiety and insomnia decreased significantly by week 4 of the
intervention period and remained significantly lower relative to control
for >18 months (between-group Cohen's d=0.63, 0.47,
0.55, respectively, at 18 months). Effects on suicidal ideation were only
short term. Two depression trajectories were identified using growth
mixture models: improving (95%) and stable/deteriorating (5%) symptoms.
More severe baseline depression, younger age and limited comfort with the
internet were associated with reduced odds of improvement.
Online CBT-I produced rapid and long-term symptom reduction in people
with subclinical depressive symptoms, although the initial effect on
suicidal ideation was not sustained.
A numerical study of the flow-induced vibration of two elastically mounted cylinders in tandem and staggered arrangements at Reynolds number
is presented. The cylinder centres are set at a streamwise distance of 1.5 cylinder diameters, placing the rear cylinder in the near-wake region of the front cylinder for the tandem arrangement. The cross-stream or lateral offset is varied between 0 and 5 cylinder diameters. The two cylinders are identical, with the same elastic mounting, and constrained to oscillate only in the cross-flow direction. The variation of flow behaviours is examined for static cylinders and for elastic mountings of a range of spring stiffnesses, or reduced velocity. At least seven major modes of flow response are identified, delineated by whether the oscillation is effectively symmetric, and the strength of the influence of the flow through the gap between the two cylinders. Submodes of these are also identified based on whether or not the flow remains periodic. More subtle temporal behaviours, such as period doubling, quasi-periodicity and chaos, are also identified and mapped. Across all of these regimes, the amplitudes of vibration and the magnitude of the fluid forces are quantified. The modes identified span the parameter space between two important limiting cases: two static bodies at varying lateral offset; and two elastically mounted bodies in a tandem configuration at varying spring stiffnesses. Some similarity in the response of extremely stiff or static bodies and extremely slack bodies is shown. This is explained by the fact that the slack bodies are free to move to an equilibrium position and stop, effectively becoming a static system. However, the most complex behaviour appears between these limits, when the bodies are in reasonably close proximity, and the natural structural frequency is close to the vortex shedding frequency of a single cylinder. This appears to be driven by the interplay between a series of time scales, including the vortex formation time, the advection time across the gap between the cylinders and the oscillation period of both bodies. This points out an important difference between this multi-body system and the classic single-cylinder vortex-induced vibration: two bodies in close proximity will not oscillate in a synchronised, periodic manner when their natural structural frequencies are close to the nominal vortex shedding frequency of a single cylinder.
In this paper, we place the Trans-Atlantic Trade and Investment Partnership (TTIP) into broader geo-political and economic context given the current Trump Administration's withdrawal from the Trans Pacific Partnership (TPP) and the loss of momentum for TTIP. Both TPP and TTIP sought to provide key tactical solutions to the particular trade/investment problems participating states faced. For the U.S. government, these free trade agreements also represented a geo-political undertaking, an attempt to once again set trade rules in light of deadlock in the WTO. Ultimately, the inability of the Obama Administration to successfully complete negotiations for and ratification of these two deals does not alter the underlying motivations that led to them in the first place. The stagnation of these deals, however, has intensified geo-economic and geo-strategic concerns: opening the door to rival articulations of trade governance and undermining U.S. credibility with its partners.
Both physical frailty and cognitive impairment predict death, but the joint effect of these two factors is uncertain. The objectives are to determine if the Mini-mental state examination (MMSE) and the Frailty Index (FI) predict death over a five-year interval after accounting for the effect of the other; and if there is an interaction in this effect.
An analysis of an existing prospective cohort study of 1,751 community living older adults followed over a five-year time frame. Age, gender, and education were self-reported. The predictor variables were the FI – a measure of frailty based on the “Accumulation of Deficits” model of frailty; and the MMSE. Cox proportional hazards models were constructed for the outcome of time to death.
The unadjusted Hazard Ratio (HR) (95% CI) for mortality was 2.17 (1.69, 2.80) for those who were only cognitively impaired, 2.02 (1.53, 2.68) for those who were only frail, and 3.57 (2.75, 4.62) for those who were both frail and cognitively impaired with the reference group of those who were neither frail nor cognitively impaired. Adjusted for age, gender, and education, the HR (95% CI) was 1.49 (1.13. 1.95) for those who were only cognitively impaired, 1.81 (1.35, 2.41) for those who were only frail, and 2.28 (1.69, 3.09) for those who were both frail and cognitively impaired.
Both frailty and cognitive impairment are predictors of mortality and the effect is cumulative. There was no interaction in this effect.