The fate of redundant cues: Further analysis of the redundancy effect

Pearce, Dopson, Haselgrove, and Esber (Journal of Experimental Psychology: Animal Behavior Processes, 38, 167–179, 2012) conducted a series of experiments with rats and pigeons in which the conditioned responding elicited by two types of redundant cue was compared. One of these redundant cues was a blocked cue X from A+ AX+ training, whereas the other was cue Y from a simple discrimination BY+ CY–. Greater conditioned responding was elicited by X than by Y; we refer to this difference as the redundancy effect. To test an explanation of this effect in terms of comparator theory (Denniston, Savastano, & Miller, 2001), a single group of rats in Experiment 1 received training of the form A+ AX+ BY+ CY–, followed by an A– Y+ discrimination. Responding to the individual cues was tested both before and after the latter discrimination. In addition to a replication of the redundancy effect during the earlier test, we observed stronger responding to B than to X, both during the earlier test and, in contradiction of the theory, after the A– Y+ discrimination. In Experiment 2, a blocking group received A+ AX+, a continuous group received AX+ BX–, and a partial group received AX± BX± training. Subsequent tests with X again demonstrated the redundancy effect, but also revealed a stronger response in the partial than in the continuous group. This pattern of results is difficult to explain with error-correction theories that assume that stimuli compete for associative strength during conditioning. We suggest, instead, that the influence of a redundant cue is determined by its relationship with the event with which it is paired, and by the attention it is paid

Surface modification of hydrophobic polymers for improvement of endothelial cell-surface interactions

The aim of this study is to improve the interaction of endothelial cells with polymers used in vascular prostheses. Polytetrafluoroethylene (PTFE; Teflon) films were treated by means of nitrogen and oxygen plasmas. Depending on the plasma exposure time, modified PTFE surfaces showed water-contact angles of 15¿58° versus 96° for unmodified PTFE. Electron spectroscopy in chemical analysis (ESCA) measurements revealed incorporation of both nitrogenand oxygen-containing groups into the PTFE surfaces, dependent on the plasma composition and exposure time. In-vitro biological evaluation of unmodified and modified PTFE surfaces showed that human endothelial cells, seeded from 20% human serum-containing culture medium, adhered well on to modified PTFE surfaces, but not on to unmodified films. Adhesion of endothelial cells on to expanded PTFE graft material (Gore-Tex) was also stimulated by plasma treatment of this substrate. On plasma-treated expanded PTFE, the adhering endothelial cells formed a monolayer, which covered the textured surface. The latter observation is important in view of the hemocompatibility of vascular grafts seeded with endothelial cells before implantation

Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: A population-based study using competing risks

© 2016 John Wiley & Sons Australia, Ltd Aim: We examined how sociodemographic, clinical and area-level factors are related to short-term prostate cancer mortality versus mortality from other causes, a crucial distinction for this disease that disproportionately affects men older than 60 years. Methods: We applied competing risk survival models to administrative data from the Queensland Cancer Registry (Australia) for men diagnosed with prostate cancer between January 2005 and July 2007, including stratification by Gleason score. Results: The men (n = 7393) in the study cohort had a median follow-up of 5 years 3 months. After adjustment, remoteness and area-level disadvantage were not significantly associated with prostate cancer mortality. However, area-level disadvantage had a significant negative relationship with hazard of death from a cause other than prostate cancer within 7 years; compared with those living in the most advantaged areas, the likelihood of mortality was higher for those in the most disadvantaged (subhazard ratio [SHR] = 1.39; 95% CI, 1.01–1.90; P = 0.041), disadvantaged (SHR = 1.51; 95% CI, 1.14–2.00; P = 0.004), middle (SHR = 1.34; 95% CI, 1.02–1.75; P = 0.034) and advantaged areas (SHR = 1.44; 95% CI, 1.09–1.89; P = 0.009). Those with Gleason score of 7 and higher had a lower hazard of prostate cancer mortality if they were living with a partner, whereas those with lower Gleason scores and living a partner had lower hazards of other-cause mortality. Conclusions: Understanding why men living in more disadvantaged areas have higher risk of non-prostate cancer mortality should be a priority

Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK

Rats distinguish between absence of events and lack of evidence in contingency learning.

The goal of three experiments was to study whether rats are aware of the difference between absence of events and lack of evidence. We used a Pavlovian extinction paradigm in which lights consistently signaling sucrose were suddenly paired with the absence of sucrose. The crucial manipulation involved the absent outcomes in the extinction phase. Whereas in the Cover conditions, access to the drinking receptacle was blocked by a metal plate, in the No Cover conditions, the drinking receptacle was accessible. The Test phase showed that in the Cover conditions, the measured expectancies of sucrose were clearly at a higher level than in the No Cover conditions. We compare two competing theories potentially explaining the findings. A cognitive theory interprets the observed effect as evidence that the rats were able to understand that the cover blocked informational access to the outcome information, and therefore the changed learning input did not necessarily signify a change of the underlying contingency in the world. An alternative associationist account, renewal theory, might instead explain the relative sparing of extinction in the Cover condition as a consequence of context change. We discuss the merits of both theories as accounts of our data and conclude that the cognitive explanation is in this case preferred

Cohort Analysis of the Association of Delirium Severity With Cerebrospinal Fluid Amyloid-Tau-Neurodegeneration Pathologies

Delirium is associated with cognitive decline and subsequent dementia, and rises in plasma total Tau (tTau) and neurofilament light (NfL), providing links to Amyloid-Tau-Neurodegeneration (ATN) pathophysiology. We investigated whether changes in delirium severity after surgery correlated with changes in cerebrospinal fluid (CSF) ATN biomarkers. Thirty-two thoracic vascular surgical patients were recruited into a prospective biomarker cohort study with assessment of delirium severity and incidence (NCT02926417). CSF (n = 54) and plasma (n = 118) samples were sent for biomarker analysis for tTau, phosphorylated tau-181 (pTau) (plasma n = 53), NfL, and amyloid-β 42/40 ratio (Ab42/40-ratio). The primary outcome was the correlation of preoperative to postoperative change in ATN biomarkers with the highest postoperative Delirium Rating Scale-98 score. CSF and plasma biomarkers all increased postoperatively (all P < .05, n = 13 paired preoperative-postoperative samples). Delirium severity was associated with peak changes in CSF tTau (P = .007, r = 0.710) and pTau (P = .01, r = 0.667) but not NfL (P = .09, rho = 0.491) or Ab42/40-ratio (P = 0.18, rho = 0.394). Sensitivity analysis with exclusion of subjects with putative spinal cord ischaemia shifted the NfL result to significance (P < .001, rho = .847). Our data show that changes in tau and biomarkers of neurodegeneration in the CSF are associated with delirium severity. These data should be considered hypothesis generating and future studies should identify if these changes are robust to confounding

Postoperative troponin increases after noncardiac surgery are associated with raised neurofilament light: a prospective observational cohort study

Background: Myocardial and neuronal injury occur commonly after noncardiac surgery. We examined whether patients who had perioperative myocardial injury (PMI) also incurred neuronal injury, and whether myocardial and neuronal injury were associated with similar changes in inflammatory markers or overlapping clinical predictors. / Methods: A total of 114 individuals >65 yr old were recruited from two ongoing perioperative cohort studies (NCT02926417; NCT03124303). Plasma samples were collected before and daily after surgery to process assays for troponin I (PMI), neurofilament light (NfL; neuronal injury) and multiplexed plasma cytokines (inflammation). The primary outcome was the change in NfL in individuals with PMI (>40 pg ml−1 increase in troponin above preoperative values). We conducted logistic regression to identify if there were shared clinical predictors for myocardial and neuronal injury. / Results: Ninety-six patients had paired NfL and troponin data. Twenty-three of 94 subjects (24%) with PMI had greater increases in NfL (median [inter-quartile range, IQR]: 29 pg ml−1 [3–95 pg ml−1]; 2.8-fold increase) compared with subjects with no troponin increase (8 pg ml−1 [3–20]; 1.3-fold increase; P=0.008). PMI was associated with increased interleukin (IL)-1ra (P=0.005), IL-2 (P=0.045), IL-8 (P=0.002), and IL-10 (P<0.001). Logistic regression showed that intraoperative hypotension was associated with PMI (P=0.043). Preoperative stroke (P=0.041) and blood loss (P=0.002), but not intraoperative hypotension, were associated with increased NfL. / Conclusions: Postoperative troponin increases were associated with changes in NfL and inflammatory cytokines. Increases in troponin, but not NfL, were associated with intraoperative hypotension, suggesting differences in the mechanisms contributing to neuronal and myocardial injury

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Impact of the Diamond Light Source on research in Earth and environmental sciences: current work and future perspectives.

Diamond Light Source Ltd celebrated its 10th anniversary as a company in December 2012 and has now accepted user experiments for over 5 years. This paper describes the current facilities available at Diamond and future developments that enhance its capacities with respect to the Earth and environmental sciences. A review of relevant research conducted at Diamond thus far is provided. This highlights how synchrotron-based studies have brought about important advances in our understanding of the fundamental parameters controlling highly complex mineral–fluid–microbe interface reactions in the natural environment. This new knowledge not only enhances our understanding of global biogeochemical processes, but also provides the opportunity for interventions to be designed for environmental remediation and beneficial use

Compliance with pathology testing guidelines in Australian general practice: Protocol for a secondary analysis of electronic health record data

© 2018 Author(s). Introduction In Australia, general practitioners usually are the first point of contact for patients with non-urgent medical conditions. Appropriate and efficient utilisation of pathology tests by general practitioners forms a key part of diagnosis and monitoring. However overutilisationand underutilisation of pathology tests have been reported across several tests and conditions, despite evidence-based guidelines outlining best practice in pathology testing. There are a limited number of studies evaluating the impact of these guidelines on pathology testing in general practice. The aim of our quantitative observational study is to define how pathology tests are used in general practice and investigate how test ordering practices align with evidence-based pathology guidelines. Methods and analysis Access to non-identifiable patient data will be obtained through electronic health records from general practices across three primary health networks in Victoria, Australia. Numbers and characteristics of patients, general practices, encounters, pathology tests and problems managed over time will be described. Overall rates of encounters and tests, alongside more detailed investigation between subcategories (encounter year, patient's age, gender, and location and general practice size), will also be undertaken. To evaluate how general practitioner test ordering coincides with evidence-based guidelines, five key candidate indicators will be investigated: Full blood counts for patients on clozapine medication; international normalised ratio measurements for patients on warfarin medication; glycated haemoglobin testing for monitoring patients with diabetes; vitamin D testing; and thyroid function testing. Ethics and dissemination Ethics clearance to collect data from general practice facilities has been obtained by the data provider from the RACGP National Research and Evaluation Ethics Committee (NREEC 17-008). Approval for the research group to use these data has been obtained from Macquarie University (5201700872). This study is funded by the Australian Government Department of Health Quality Use of Pathology Program (Agreement ID: 4-2QFVW4M). Findings will be reported to the Department of Health and disseminated in peer-reviewed academic journals and presentations (national and international conferences, industry forums)