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An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs.
A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost–consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered.
In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs.
The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty—prevalence in this patient population and referral behavior.
Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function.
The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning.
Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks.
These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Speleothem organic matter can be a powerful tracer for past environmental conditions and karst processes. Carbon isotope measurements (δ13C and 14C) in particular can provide crucial information on the provenance and age of speleothem organic matter, but are challenging due to low concentrations of organic matter in stalagmites. Here, we present a method development study on extraction and isotopic characterization of speleothem organic matter using a rapid procedure with low laboratory contamination risk. An extensive blank assessment allowed us to quantify possible sources of contamination through the entire method. Although blank contamination is consistently low (1.7 ± 0.34 – 4.3 ± 0.86 μg C for the entire procedure), incomplete sample decarbonation poses a still unresolved problem of the method, but can be detected when considering both δ13C and 14C values. We test the method on five stalagmites, showing reproducible results on samples as small as 7 μg C for δ13C and 20 μg C for 14C. Furthermore, we find consistently lower non-purgeable organic carbon (NPOC) 14C values compared to the carbonate 14C over the bomb spike interval in two stalagmites from Yok Balum Cave, Belize, suggesting overprint of a pre-aged or even fossil source of carbon on the organic fraction incorporated by these stalagmites.
Weed removal experiments in dry edible beans were conducted during 1992 and 1993 at Crookston and Staples, MN. Ten manual weed removal treatments were studied to determine when a natural infestation of weeds first reduced dry bean yield, and when weed removal could be discontinued without further loss of seed yield. Major weeds in order of average biomass production on weedy check plots at dry bean harvest over locations and years were wild mustard, foxtail spp., redroot pigweed, common ragweed, wild buckwheat, hairy nightshade, and common lambsquarters. Hairy nightshade also emerged late in the growing season and could negatively affect harvest efficiency and stain navy beans. Weed removal treatments had little effect on dry bean stands or 100-seed weights of harvested dry bean seed. The critical period for weed control in dry beans was 3 to 5 or 6 weeks after planting (WAP). Thus, weed control practices should begin no later than 3 WAP and continue until at least 5 or 6 WAP for maximum dry bean yields.
Ageing is associated with a prolonged and exaggerated postprandial lipaemia. This study aimed to examine the contribution of alterations in chylomicron synthesis, size and lipid composition to increased lipaemia. Healthy older (60–75 years; n 15) and younger (20–25 years; n 15) subjects consumed a high-fat breakfast. Chylomicron dynamics and fatty acid composition were analysed for 5 h in the postprandial state. Plasma TAG levels were elevated following the meal in the older subjects, relative to younger subjects (P<0·01). For older subjects compared with younger subjects, circulating chylomicron particle size was smaller (P<0·05), with greater apoB content (P<0·05) at all postprandial time points. However, total chylomicron TAG concentration between the groups was unaltered post-meal. Compared with younger subjects, the older subjects exhibited a greater proportion of oleic acid in the TAG and phospholipid (PL) fraction (P<0·05), plus lower proportions of linoleic acid in the TAG fraction of the chylomicrons (P<0·01). Thus, following the ingestion of a high-fat meal, older individuals demonstrate both smaller, more numerous chylomicrons, with a greater total MUFA and lower PUFA contents. These data suggest that the increased postprandial lipaemia of ageing cannot be attributed to increased chylomicron TAG. Rather, ageing is associated with changes in chylomicron particle size, apoB content and fatty acid composition of the chylomicron TAG and PL fractions.
The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae, and orphan afterglows of gamma-ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of 5 s and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.
Four sampling methods for Ooencyrtus kuvanae (Howard) populations were compared for efficiency using coefficients of variation. On this basis, none of the sampling methods was uniformly superior to any other, but a cluster of 0.01 ha subplots was chosen as the best method because of the aggregation of both gypsy moth egg masses and parasitoids. From the estimated population variance per egg mass it was calculated that 150 egg masses should be sampled per plot to provide an error bound of 0.2 parasitoid per egg mass (α = 0.1). An analysis of variance indicated that variation among study areas was the largest source of variation, and that among day, within day, and plot configuration variation were significant. Estimates of parasitoid activity are most reliable during the period between 1300 and 1600 h EST. Activity of parasitoids was reduced on overcast days. In August, the distribution of O. kuvanae approximates that of the negative binomial but with too many individuals in the high frequency classes. In a compromise between cost and accuracy, the sampling scheme selected consists of thirty 0.01 ha subplots per plot sampled between 1300 and 1600 h EST on sunny days. This sampling scheme was found satisfactory using field evaluation.
To determine Canadian emergency physicians’ estimates regarding the safety and efficiency of chest discomfort management in their emergency department (ED), and their attitudes toward and perception of the need for a chest discomfort clinical prediction rule that identifies very low risk patients who are safe to discharge after a brief ED assessment.
300 members of the Canadian Association of Emergency Physicians (CAEP) were randomly selected to receive a confidential mail survey, which invited them to provide information on current disposition of patients with chest discomfort and their opinions regarding the value of a clinical prediction rule to identify patients with chest discomfort who are safe to discharge after a brief (~2 hour) assessment.
Of the 300 physicians selected, 288 were eligible for the survey and 235 (82%) responded. Only 5% follow discharged patients to measure safe practice. Overall, 165 (70%) felt the proposed prediction rule would be very useful and 43 (18%) felt it would be useful. Almost all (94%) believed a prediction rule would be useful if it identified patients safe for discharge without increasing the current rate of missed acute myocardial infarction (estimated at 2%). Most respondents (59%) believed that a clinical prediction rule should suggest a course of action, while 30% felt it should convey a probability of disease.
Canadian emergency physicians support the concept of a clinical prediction rule for the early discharge of patients with chest discomfort. Most believe that such a rule would be useful if it identified patients who are safe for discharge after a brief assessment, while maintaining current levels of safety. Future research should be aimed at deriving a clinical prediction rule to identify low risk patients who can be safely discharged after a limited emergency department evaluation.
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