Visual binding, reentry, and neuronal synchrony in a physically situated brain-based device

By constructing and analyzing a physically situated brain-based device (i.e. a device with sensors and actuators whose behavior is guided by a simulated nervous system), we show that reentrant connectivity and dynamic synchronization can provide an effective mechanism for binding the visual features of objects

In memoriam, a Scottish Eulogy: David A.R. Forrester (1928-2009); American Memorial to David A.R. Forrester;

David Alexander Roxburgh Forrester passed away on April 21, 2009, at age 81. Forrester, a Scotsman, was an honorary life member of the Academy of Accounting Historians and a winner of the Academy\u27s Hourglass Award in 1978 for his book entitled Schmalenbach and After: A Study of the Evolution of German Business Economics

New Insights into the Generation of CD4 Memory May Shape Future Vaccine Strategies for Influenza

Influenza viral evolution presents a formidable challenge to vaccination due to the virus\u27 ability to rapidly mutate to evade immune responses. Live influenza infections generate large and diverse CD4 effector T cell responses that yield highly protective, long-lasting CD4 T cell memory that can target conserved viral epitopes. We review advances in our understanding of mechanisms involved in generating CD4 T cell responses against the influenza A virus (IAV), focusing on specialized follicular helper (TFH) and CD4 cytotoxic (ThCTL) effector subsets and on CD4 T cell memory. We also discuss two recent findings in context of enhancing vaccine responses. First, helper T cells require priming with APC secreting high levels of IL-6. Second, the transition of IAV-generated effectors to memory depends on IL-2, costimulation and antigen signals, just before effectors reach peak numbers, defined as the memory checkpoint. The need for these signals during the checkpoint could explain why many current influenza vaccines are poorly effective and elicit poor cellular immunity. We suggest that CD4 memory generation can be enhanced by re-vaccinating at this time. Our best hope lies in a universal vaccine that will not need to be formulated yearly against seasonal antigenically novel influenza strains and will also be protective against a pandemic strain. We suggest a vaccine approach that elicits a powerful T cell response, by initially inducing high levels of APC activation and later providing antigen at the memory checkpoint, may take us a step closer to such a universal influenza vaccine

Protocol for the Reconstructing Consciousness and Cognition (ReCCognition) Study

Important scientific and clinical questions persist about general anesthesia despite the ubiquitous clinical use of anesthetic drugs in humans since their discovery. For example, it is not known how the brain reconstitutes consciousness and cognition after the profound functional perturbation of the anesthetized state, nor has a specific pattern of functional recovery been characterized. To date, there has been a lack of detailed investigation into rates of recovery and the potential orderly return of attention, sensorimotor function, memory, reasoning and logic, abstract thinking, and processing speed. Moreover, whether such neurobehavioral functions display an invariant sequence of return across individuals is similarly unknown. To address these questions, we designed a study of healthy volunteers undergoing general anesthesia with electroencephalography and serial testing of cognitive functions (NCT01911195). The aims of this study are to characterize the temporal patterns of neurobehavioral recovery over the first several hours following termination of a deep inhaled isoflurane general anesthetic and to identify common patterns of cognitive function recovery. Additionally, we will conduct spectral analysis and reconstruct functional networks from electroencephalographic data to identify any neural correlates (e.g., connectivity patterns, graph-theoretical variables) of cognitive recovery after the perturbation of general anesthesia. To accomplish these objectives, we will enroll a total of 60 consenting adults aged 20–40 across the three participating sites. Half of the study subjects will receive general anesthesia slowly titrated to loss of consciousness (LOC) with an intravenous infusion of propofol and thereafter be maintained for 3 h with 1.3 age adjusted minimum alveolar concentration of isoflurane, while the other half of subjects serves as awake controls to gauge effects of repeated neurobehavioral testing, spontaneous fatigue and endogenous rest-activity patterns

Implementing telephone triage in general practice: a process evaluation of a cluster randomised controlled trial

Background: Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. However, limited evidence exists of the challenges GP practices face in implementing telephone triage. We conducted a qualitative process evaluation alongside a UK-based cluster randomised trial (ESTEEM) which compared the impact of GP-led and nurse-led telephone triage with usual care on primary care workload, cost, patient experience, and safety for patients requesting a same-day GP consultation. The aim of the process study was to provide insights into the observed effects of the ESTEEM trial from the perspectives of staff and patients, and to specify the circumstances under which triage is likely to be successfully implemented. Here we report perspectives of staff. Methods: The intervention comprised implementation of either GP-led or nurse-led telephone triage for a period of 2-3 months. A qualitative evaluation was conducted using staff interviews recruited from eight general practices (4 GP triage, 4 Nurse triage) in the UK, implementing triage as part of the ESTEEM trial. Qualitative interviews were undertaken with 44 staff members in GP triage and nurse triage practices (16 GPs, 8 nurses, 7 practice managers, 13 administrative staff). Results: Staff reported diverse experiences and perceptions regarding the implementation of telephone triage, its effects on workload, and on the benefits of triage. Such diversity were explained by the different ways triage was organised, the staffing models used to support triage, how the introduction of triage was communicated across practice staff, and by how staff roles were reconfigured as a result of implementing triage. Conclusion: The findings from the process evaluation offer insight into the range of ways GP practices participating in ESTEEM implemented telephone triage, and the circumstances under which telephone triage can be successfully implemented beyond the context of a clinical trial. Staff experiences and perceptions of telephone triage are shaped by the way practices communicate with staff, prepare for and sustain the changes required to implement triage effectively, as well as by existing practice culture, and staff and patient behaviour arising in response to the changes made. Trial registration: Current Controlled Trials ISRCTN20687662. Registered 28 May 2009

Rapid default transition of CD4 T cell effectors to functional memory cells

The majority of highly activated CD4 T cell effectors die after antigen clearance, but a small number revert to a resting state, becoming memory cells with unique functional attributes. It is currently unclear when after antigen clearance effectors return to rest and acquire important memory properties. We follow well-defined cohorts of CD4 T cells through the effector-to-memory transition by analyzing phenotype, important functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 d closely resemble canonical memory cells rested for 60 d or longer in the absence of antigen. This is true for both Th1 and Th2 lineages, and occurs whether CD4 T cell effectors rest in vivo or in vitro, suggesting a default pathway. We find that the effector–memory transition at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a cohort of genes uniquely associated with memory cells rested for extended periods

Structural Characterization of a High-Temperature, Ionic Conducting Ceramic using Perturbed Angular Correlation Spectroscopy

Perturbed angular correlation (PAC) spectroscopy has been used to characterize several structural aspects of a high-temperature, ionic conducting ceramic, CaZr3.95Hf0.05P6O24. Hafnium was introduced into the material to provide the PAC probe nuclei, 181Hf/181Ta, which were located primarily at Zr sites. PAC measurements were made over a range of temperatures from 77 to 1180 K, and they have been analyzed and interpreted using several simple models. The distorted octahedral crystal field at the Zr site produced a (low-frequency) static electric quadrupole interaction which can be accurately described by the point-charge model. But, the temperature dependence of the associated electric field gradient (EFG) cannot be described accurately by purely static considerations via the point-charge model and high-temperature x-ray diffraction data. Although a high-frequency static interaction was also observed, the measurements were not sufficiently accurate to identify its origin unambiguously. Some of the high-temperature measurements show evidence of a time-varying interaction, which may result from Ca2+-ion jumping. But, jump frequencies derived classically from high-temperature electrical dc conductivity measurements are too low to agree with those indicated by the PAC data. However, the dc conductivity measurements support a simple model of thermally activated Ca2+-ion transport. The temperature dependence of the EFG (corresponding to the low-frequency interaction) was used to determine an effective Debye-Waller factor. As a result of using this approach to analyze this type of PAC data, this factor was shown also to agree qualitatively with the predictions of the Debye crystal model, although significant theoretical limitations were encountered. These particular results suggest that the PAC technique may provide new insights into understanding advanced ceramic materials