Novelty Enhances Visual Perception

The effects of novelty on low-level visual perception were investigated in two experiments using a two-alternative forced-choice tilt detection task. A target, consisting of a Gabor patch, was preceded by a cue that was either a novel or a familiar fractal image. Participants had to indicate whether the Gabor stimulus was vertically oriented or slightly tilted. In the first experiment tilt angle was manipulated; in the second contrast of the Gabor patch was varied. In the first, we found that sensitivity was enhanced after a novel compared to a familiar cue, and in the second we found sensitivity to be enhanced for novel cues in later experimental blocks when participants became more and more familiarized with the familiar cue. These effects were not caused by a shift in the response criterion. This shows for the first time that novel stimuli affect low-level characteristics of perception. We suggest that novelty can elicit a transient attentional response, thereby enhancing perception

Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability

Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening

Searching for the Majority: Algorithms of Voluntary Control

Voluntary control of information processing is crucial to allocate resources and prioritize the processes that are most important under a given situation; the algorithms underlying such control, however, are often not clear. We investigated possible algorithms of control for the performance of the majority function, in which participants searched for and identified one of two alternative categories (left or right pointing arrows) as composing the majority in each stimulus set. We manipulated the amount (set size of 1, 3, and 5) and content (ratio of left and right pointing arrows within a set) of the inputs to test competing hypotheses regarding mental operations for information processing. Using a novel measure based on computational load, we found that reaction time was best predicted by a grouping search algorithm as compared to alternative algorithms (i.e., exhaustive or self-terminating search). The grouping search algorithm involves sampling and resampling of the inputs before a decision is reached. These findings highlight the importance of investigating the implications of voluntary control via algorithms of mental operations

Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an

Early detection of left ventricular diastolic dysfunction in Chagas' disease

BACKGROUND: Chagas' disease may cause left ventricular diastolic dysfunction and its early detection in asymptomatic patients would allow to stratify the risk and to optimize medical treatment. The aim of this study is to investigate if transmitral Doppler flow can detect early abnormalities of the diastolic left ventricular function in patients during the indeterminate phase of Chagas' disease, in which the electrocardiogram (ECG), chest x-ray and 2-D echocardiogram (2D-echo) are normal. METHODS: a group of 54 patients with Chagas' disease was studied and compared to a control group of 27 subjects of similar age. All were assessed with an ECG, chest X-ray, 2-D echo, and transmitral Doppler flow. RESULTS: both groups had similar values in the 2D-echo. In patients with Chagas' disease, the transmitral Doppler showed a higher peak A velocity (control group: 0.44 m/sec, Chagas group: 0.55 m/sec, p = 0.001), a lower E/A ratio (control group: 1.45, Chagas group: 1.22, p < 0.05), and a lengthening of the deceleration time of early diastolic filling (control: 138.7 ± 26.8 msec, Chagas group: 167.9 ± 34.6 msec, p = 001), thus revealing an early disorder of the diastolic left ventricular function in patients with Chagas' disease. CONCLUSION: in patients with Chagas' disease who are in the indeterminate phase, transmitral Doppler flow allowed to identify early abnormalities of the left ventricular diastolic function, which provide useful clinical information for prognostic stratification and treatment

The updating of clinical practice guidelines: insights from an international survey

Contains fulltext : 98466.pdf (publisher's version ) (Open Access)BACKGROUND: Clinical practice guidelines (CPGs) have become increasingly popular, and the methodology to develop guidelines has evolved enormously. However, little attention has been given to the updating process, in contrast to the appraisal of the available literature. We conducted an international survey to identify current practices in CPG updating and explored the need to standardize and improve the methods. METHODS: We developed a questionnaire (28 items) based on a review of the existing literature about guideline updating and expert comments. We carried out the survey between March and July 2009, and it was sent by email to 106 institutions: 69 members of the Guidelines International Network who declared that they developed CPGs; 30 institutions included in the U.S. National Guideline Clearinghouse database that published more than 20 CPGs; and 7 institutions selected by an expert committee. RESULTS: Forty-four institutions answered the questionnaire (42% response rate). In the final analysis, 39 completed questionnaires were included. Thirty-six institutions (92%) reported that they update their guidelines. Thirty-one institutions (86%) have a formal procedure for updating their guidelines, and 19 (53%) have a formal procedure for deciding when a guideline becomes out of date. Institutions describe the process as moderately rigorous (36%) or acknowledge that it could certainly be more rigorous (36%). Twenty-two institutions (61%) alert guideline users on their website when a guideline is older than three to five years or when there is a risk of being outdated. Twenty-five institutions (64%) support the concept of "living guidelines," which are continuously monitored and updated. Eighteen institutions (46%) have plans to design a protocol to improve their guideline-updating process, and 21 (54%) are willing to share resources with other organizations. CONCLUSIONS: Our study is the first to describe the process of updating CPGs among prominent guideline institutions across the world, providing a comprehensive picture of guideline updating. There is an urgent need to develop rigorous international standards for this process and to minimize duplication of effort internationally

Adaptive hybrid robotic system for rehabilitation of reaching movement after a brain injury: a usability study

BACKGROUND: Brain injury survivors often present upper-limb motor impairment affecting the execution of functional activities such as reaching. A currently active research line seeking to maximize upper-limb motor recovery after a brain injury, deals with the combined use of functional electrical stimulation (FES) and mechanical supporting devices, in what has been previously termed hybrid robotic systems. This study evaluates from the technical and clinical perspectives the usability of an integrated hybrid robotic system for the rehabilitation of upper-limb reaching movements after a brain lesion affecting the motor function. METHODS: The presented system is comprised of four main components. The hybrid assistance is given by a passive exoskeleton to support the arm weight against gravity and a functional electrical stimulation device to assist the execution of the reaching task. The feedback error learning (FEL) controller was implemented to adjust the intensity of the electrical stimuli delivered on target muscles according to the performance of the users. This control strategy is based on a proportional-integral-derivative feedback controller and an artificial neural network as the feedforward controller. Two experiments were carried out in this evaluation. First, the technical viability and the performance of the implemented FEL controller was evaluated in healthy subjects (N = 12). Second, a small cohort of patients with a brain injury (N = 4) participated in two experimental session to evaluate the system performance. Also, the overall satisfaction and emotional response of the users after they used the system was assessed. RESULTS: In the experiment with healthy subjects, a significant reduction of the tracking error was found during the execution of reaching movements. In the experiment with patients, a decreasing trend of the error trajectory was found together with an increasing trend in the task performance as the movement was repeated. Brain injury patients expressed a great acceptance in using the system as a rehabilitation tool. CONCLUSIONS: The study demonstrates the technical feasibility of using the hybrid robotic system for reaching rehabilitation. Patients’ reports on the received intervention reveal a great satisfaction and acceptance of the hybrid robotic system

Regulation of RasGRP1 Function in T Cell Development and Activation by Its Unique Tail Domain

The Ras-guanyl nucleotide exchange factor RasGRP1 plays a critical role in T cell receptor-mediated Erk activation. Previous studies have emphasized the importance of RasGRP1 in the positive selection of thymocytes, activation of T cells, and control of autoimmunity. RasGRP1 consists of a number of well-characterized domains, which it shares with its other family members; however, RasGRP1 also contains an ∼200 residue-long tail domain, the function of which is unknown. To elucidate the physiological role of this domain, we generated knock-in mice expressing RasGRP1 without the tail domain. Further analysis of these knock-in mice showed that thymocytes lacking the tail domain of RasGRP1 underwent aberrant thymic selection and, following TCR stimulation, were unable to activate Erk. Furthermore, the deletion of the tail domain led to enhanced CD4+ T cell expansion in aged mice, as well as the production of autoantibodies. Mechanistically, the tail-deleted form of RasGRP1 was not able to traffic to the cell membrane following stimulation, indicating a potential reason for its inability to activate Erk. While the DAG-binding C1 domain of RasGRP1 has long been recognized as an important factor mediating Erk activation, we have revealed the physiological relevance of the tail domain in RasGRP1 function and control of Erk signaling

Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1

This work was funded by Arthritis Research UK. MJL holds an Arthritis Research UK Clinician Scientist Fellowship (19631), and was previously supported by the St Thomas’ Lupus Trust. The study received support from the National Institute for Health Research (NIHR)-funded Flow Cytometry Core Facility and the Biomedical Research Centre based at Guy’s & St. Thomas’ National Health Service (NHS) Foundation Trust, in partnership with King’s College London

Is every strong lens model unhappy in its own way? Uniform modelling of a sample of 13 quadruply+ imaged quasars

Strong-gravitational lens systems with quadruply imaged quasars (quads) are unique probes to address several fundamental problems in cosmology and astrophysics. Although they are intrinsically very rare, ongoing and planned wide-field deep-sky surveys are set to discover thousands of such systems in the next decade. It is thus paramount to devise a general framework to model strong-lens systems to cope with this large influx without being limited by expert investigator time. We propose such a general modelling framework (implemented with the publicly available software LENSTRONOMY) and apply it to uniformly model three-band Hubble Space Telescope Wide Field Camera 3 images of 13 quads. This is the largest uniformly modelled sample of quads to date and paves the way for a variety of studies. To illustrate the scientific content of the sample, we investigate the alignment between the mass and light distribution in the deflectors. The position angles of these distributions are well-aligned, except when there is strong external shear. However, we find no correlation between the ellipticity of the light and mass distributions. We also show that the observed flux-ratios between the images depart significantly from the predictions of simple smooth models. The departures are strongest in the bluest band, consistent with microlensing being the dominant cause in addition to millilensing. Future papers will exploit this rich data set in combination with ground-based spectroscopy and time delays to determine quantities such as the Hubble constant, the free streaming length of dark matter, and the normalization of the initial stellar mass function