We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Plotinus' Enneads is a work which is central to the history of philosophy in late antiquity. This is the second edition of the first English translation of the complete works of Plotinus in one volume in seventy years, which also includes Porphyry's Life of Plotinus. Led by Lloyd P. Gerson, a team of experts present up-to-date translations which are based on the best available text, the edition minor of Henry and Schwyzer and its corrections. The translations are consistent in their vocabulary, making the volume ideal for the study of Plotinus' philosophical arguments. This second edition includes a number of corrections, as well as additional cross-references to enrich the reader's understanding of Plotinus' sometimes very difficult presentation of his ideas. It will be invaluable for scholars of Plotinus with or without ancient Greek, as well as for students of the Platonic tradition.
There is a clinical need to appropriately apply large language model (LLM)-based systems for use in infectious diseases. We sought to use LLM and machine learning for extracting antibiotic susceptibility from clinical microbiology free-text reports, allowing use for outbreak detection, increasing information gathering efficiency, and public health reporting.
Just before World War I, the Hudson’s Bay Company (HBC) geographically expanded its trade in the Canadian Arctic to derive profits from Arctic fox fur and secure its position in a global value chain (GVC) delivering fur to metropolitan consumers. The “problem of nature” challenged the company’s business venture. Furthermore, “nature” was made and remade by the HBC’s own capital investments. The fox trade itself changed human ecology. Technology transfers to Inuit modified their hunting regimes to increase the company’s returns of polar bear skins. Though these skins had high potential market value, modes of production introduced by the HBC to the Arctic precluded the company from sending high-quality products to metropolitan dressers. Within a changing Arctic human ecology, the HBC produced one highly valued commodity for the market while producing another from which it could derive only modest profit. The HBC’s fox and polar bear trade at the onset of the last century suggests ways that business empires can set off complex and unanticipated changes in human ecologies and, therefore, the dynamics of nature and business at their very peripheries.
We consider pricing of a specialised critical illness and life insurance contract for breast cancer (BC) risk. We compare (a) an industry-based Markov model with (b) a recently developed semi-Markov model, which accounts for unobserved BC cases and progression through clinical stages of BC, and (c) an alternative Markov model derived from (b). All models are calibrated using population data in England and data from the medical literature. We show that the semi-Markov model aligns best with empirical evidence. We then consider net premiums of specialized life insurance products under various scenarios of cancer diagnosis and treatment. The results show strong dependence on the time spent with diagnosed or undiagnosed pre-metastatic BC. This proves to be significant for refining cancer survival estimates and accurately estimating related age dependence by cancer stage. In contrast, the industry-based model, by overlooking this critical factor, is more sensitive to the model assumptions, underscoring its limitations in cancer estimates.
The proscription of organisations has long been a central feature of legal regimes aimed at the suppression of terrorism. Australia is no exception. Going back many decades, the Commonwealth government has sought to meet the threat of political violence through the proscription of related organisations. In the wake of the September 11 terrorist strikes against New York and Washington, renewed efforts were made for the proscription of organisations in many national jurisdictions (for example, the United Kingdom, United States and Canada) as well as at the international level (for example, through the United Nations and the European Union.
In Australia, the Commonwealth looked directly to the justifications offered by the United Kingdom’s Lord Lloyd of Berwick and Paul Wilkinson just a few years before. In their major Inquiry into Legislation Against Terrorism, Lord Lloyd and Wilkinson presented three principal rationales to explain the role of proscription in the prevention of terrorism: ease of proof; providing a basis for the criminalisation of fundraising and other activities of terrorist groups; and as a clear symbol of ‘public revulsion and reassurance that severe measures [are] being taken’.
Williams v Commonwealth of Australia is a landmark decision of the High Court on the scope of federal executive power in s 61 of the Constitution. The decision is also important for the interpretive methodology adopted by the Court. Notably, each judge based their understanding of s 61 upon federal readings of the Constitution. This methodology raises fresh questions about how the Constitution is to be interpreted, and whether Williams marks a break from orthodox understandings of that task. This article assesses the significance of Williams for constitutional interpretation in Australia, and whether it lays the foundation for a more robust protection of state interests by the High Court.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Fast radio bursts (FRBs) are short-duration radio transients that occur at random times in host galaxies distributed all over the sky. Large field of view instruments can play a critical role in the blind search for rare FRBs. We present a concept for an all-sky FRB monitor using a compact all-sky phased array (CASPA), which can efficiently achieve an extremely large field of view of $\sim10^4$ square degrees. Such a system would allow us to conduct a continuous, blind FRB search covering the entire southern sky. Using the measured FRB luminosity function, we investigate the detection rate for this all-sky phased array and compare the result to a number of other proposed large field-of-view instruments. We predict a rate of a few FRB detections per week and determine the dispersion measure and redshift distributions of these detectable FRBs. This instrument is optimal for detecting FRBs in the nearby Universe and for extending the high-end of the FRB luminosity function through finding ultraluminous events. Additionally, this instrument can be used to shadow the new gravitational-wave observing runs, detect high-energy events triggered from Galactic magnetars and search for other bright, but currently unknown transient signals.
We present the Sydney Radio Star Catalogue, a new catalogue of stars detected at megahertz to gigahertz radio frequencies. It consists of 839 unique stars with 3 405 radio detections, more than doubling the previously known number of radio stars. We have included stars from large area searches for radio stars found using circular polarisation searches, cross-matching, variability searches, and proper motion searches as well as presenting hundreds of newly detected stars from our search of Australian SKA Pathfinder observations. The focus of this first version of the catalogue is on objects detected in surveys using SKA precursor and pathfinder instruments; however, we will expand this scope in future versions. The 839 objects in the Sydney Radio Star Catalogue are distributed across the whole sky and range from ultracool dwarfs to Wolf-Rayet stars. We demonstrate that the radio luminosities of cool dwarfs are lower than the radio luminosities of more evolved sub-giant and giant stars. We use X-ray detections of 530 radio stars by the eROSITA soft X-ray instrument onboard the Spectrum Roentgen Gamma spacecraft to show that almost all of the radio stars in the catalogue are over-luminous in the radio, indicating that the majority of stars at these radio frequencies are coherent radio emitters. The Sydney Radio Star Catalogue can be found in Vizier or at https://radiostars.org.
Functional decline following hospitalization remains an important problem in health care, especially for frail older adults. Modifiable factors related to reduction in harms of hospitalization are not well described. One particularly pervasive factor is emergency department (ED) boarding time; time waiting from decision to admit, until transfer to an in-patient medical unit. We sought to investigate how the functional status of frail older adults correlated with the length of time spent boarded in the ED. We found that patients who waited for 24 hours or more exhibited functional decline in both the Barthel Index and Hierarchical Assessment of Balance and Mobility and an increase in the Clinical Frailty Scale from discharge to 6 months post discharge. In conclusion, there is a need for additional investigation into ED focused interventions to reduce ED boarding time for this population or to improve access to specialized geriatric services within the ED.
OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.
Biodesign is a relatively new interdisciplinary field, which has grown rapidly over the last decade (as evidenced for example by the growth in student teams entering the Biodesign Challenge from 9 in 2016 to 52 in 2024).
Soil amelioration via strategic deep tillage is occasionally utilized within conservation tillage systems to alleviate soil constraints, but its impact on weed seed burial and subsequent growth within the agronomic system is poorly understood. This study assessed the effects of different strategic deep-tillage practices, including soil loosening (deep ripping), soil mixing (rotary spading), or soil inversion (moldboard plow), on weed seed burial and subsequent weed growth, compared with a no-till control. The tillage practices were applied in 2019 at Yerecoin and Darkan, WA, and data on weed seed burial and growth were collected during the following 3-yr winter crop rotation (2019 to 2021). Soil inversion buried 89% of rigid ryegrass (Lolium rigidum Gaudin) and ripgut brome (Bromus diandrus Roth) seeds to a depth of 10 to 20 cm at both sites, while soil loosening and mixing left between 31% and 91% of the seeds in the top 0 to 10 cm of soil, with broad variation between sites. Few seeds were buried beyond 20 cm despite tillage working depths exceeding 30 cm at both sites. Soil inversion reduced the density of L. rigidum to <1 plant m−2 for 3 yr after strategic tillage. Bromus diandrus density was initially reduced to 0 to 1 plant m−2 by soil inversion, but increased to 4 plants m−2 at Yerecoin in 2020 and 147 plants at Darkan in 2021. Soil loosening or mixing did not consistently decrease weed density. The field data were used to parameterize a model that predicted weed density following strategic tillage with greater accuracy for soil inversion than for loosening or mixing. The findings provide important insights into the effects of strategic deep tillage on weed management in conservational agricultural systems and demonstrate the potential of models for optimizing weed management strategies.
Automatic dialog systems have become a mainstream part of online customer service. Many such systems are built, maintained, and improved by customer service specialists, rather than dialog systems engineers and computer programmers. As conversations between people and machines become commonplace, it is critical to understand what is working, what is not, and what actions can be taken to reduce the frequency of inappropriate system responses. These analyses and recommendations need to be presented in terms that directly reflect the user experience rather than the internal dialog processing.
This paper introduces and explains the use of Actionable Conversational Quality Indicators (ACQIs), which are used both to recognize parts of dialogs that can be improved and to recommend how to improve them. This combines benefits of previous approaches, some of which have focused on producing dialog quality scoring while others have sought to categorize the types of errors the dialog system is making. We demonstrate the effectiveness of using ACQIs on LivePerson internal dialog systems used in commercial customer service applications and on the publicly available LEGOv2 conversational dataset. We report on the annotation and analysis of conversational datasets showing which ACQIs are important to fix in various situations.
The annotated datasets are then used to build a predictive model which uses a turn-based vector embedding of the message texts and achieves a 79% weighted average f1-measure at the task of finding the correct ACQI for a given conversation. We predict that if such a model worked perfectly, the range of potential improvement actions a bot-builder must consider at each turn could be reduced by an average of 81%.
The coefficient of friction of clay minerals at the micro-scale has generally not been studied due to difficulties in obtaining measurements in a bulk-soil volume undergoing shear at such small scales. Information on friction at the micro-scale may provide insight into grain-scale processes that operate in bulk samples or in natural faults. The objective of this study was to develop a method to measure the microscale friction coefficient of smectites. The experiments described show that the axial atomic force microscopy method can be adapted to easily obtain accurate coefficient of friction (μ) measurements for smectites from force curves involving colloidal probes. The method allows for the measurements to be performed over spatial scales of a few μm, can be carried out under dry conditions or a wide range of aqueous solutions, and requires no calibration beyond making a few microscopic measurements of the probe. This method provides measurements of micro-scale normal and shear forces between minerals, which can be used for a variety of applications such as the study of shear deformation, consolidation, and fault dynamics. Control tests of silica on mica (μ = 0.29±0.02) agree with literature values where limits indicate one standard deviation. Coefficient of friction values for wet and dry Na-montmorillonite were determined to be 0.20±0.03 and 0.72±0.03, respectively.
Women have a greater lifetime risk of developing Alzheimer’s disease (AD) dementia than men, a sex/gender disparity that cannot be explained by female longevity alone. There is substantial evidence for sex differences in the effects of APOE £4 on risk for AD. While APOE e4 increases AD risk in both sexes, women who carry APOE e4 are disproportionately vulnerable to cognitive impairment and AD compared to their counterpart men. In contrast to APOE e4, APOE £2 is associated with slower cognitive decline and a lower risk of AD. Although a less robust literature, APOE e2 may also have sex-specific effects. Because APOE e2 is the rarest major APOE allele, well-powered studies are needed to examine sex-specific effects. The objective of the present study was to examine sex-specific associations of APOE e2 carriage with longitudinal cognitive decline in a large cohort of clinically unimpaired adults.
Participants and Methods:
We used observational data from two sources: the National Alzheimer’s Coordinating Center (NACC) and the Rush Alzheimer’s Disease Center (ROS/MAP/MARS) studies. We included data from clinically unimpaired adults who were >50 years old at baseline who self-identified as non-Hispanic White (NHW) or non-Hispanic Black (NHB). Participants were categorized as APOE £2, £4, or £3/e3 carriers. APOE e2/e4 carriers were excluded. The same battery of neuropsychological tests was used to assess global cognition in participants from both data sources. Linear mixed models examined interactive associations of genotype (£2 or £4 vs. £3/£3), sex, and time on longitudinal cognition in NHW and NHB participants separately. Analyses were first performed in a pooled sample of NACC and ROS/MAP/MARS participants and if significant they were repeated separately in each data source.
Results:
Across both data sources, 9,766 NHW (mean (SD) age=73.0(9.00) years, mean (SD) education=16.3(2.83) years, n(%) women=6,344(65.0)) and 2,010 NHB participants (mean(SD) age=71.3(7.59) years, mean(SD) education=14.9(3.10) years, n(%) women=1,583(78.8)) met inclusion criteria. Sex modified the association between APOE £2 and cognitive decline in NHW (ß=0.097, 95% CI: 0.023-0.172, pint=.01) but not NHB participants (ß=-0.011, 95% CI: -0.153-0.131, pint=.9). In sex-stratified analyses of NHW participants, APOE £2 (vs. £3/£3) carriage was associated with attenuated cognitive decline in men (ß=0.096, 95% CI: 0.037-0.155, p=.001), but not women (ß=-0.001, 95% CI: -0.044-0.043, p=.97). In analyses comparing men and women APOE £2 carriers, men exhibited slower cognitive decline than women (ß=0.120, 95% CI: 0.051-0.190, p=.001). Analyses performed separately in NACC and ROS/MAP revealed the same pattern of male-specific APOE £2 protection in NHW participants in both data sources.
Conclusions:
In light of the longstanding view that APOE £2 protects against AD and dementia, our results provide evidence that APOE £2 is associated with attenuated cognitive decline in men but not women among NHW adults. This male-specific protection may contribute to sex differences in AD-related cognitive decline. Our findings have important implications for understanding the biological drivers of sex differences in AD risk, which is crucial for developing sex-specific strategies to prevent and treat AD dementia.
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:
48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:
Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:
After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.
Participants and Methods:
336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.
Results:
ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).
Conclusions:
To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.