Adaptation and Selective Information Transmission in the Cricket Auditory Neuron AN2

Sensory systems adapt their neural code to changes in the sensory environment, often on multiple time scales. Here, we report a new form of adaptation in a first-order auditory interneuron (AN2) of crickets. We characterize the response of the AN2 neuron to amplitude-modulated sound stimuli and find that adaptation shifts the stimulus–response curves toward higher stimulus intensities, with a time constant of 1.5 s for adaptation and recovery. The spike responses were thus reduced for low-intensity sounds. We then address the question whether adaptation leads to an improvement of the signal's representation and compare the experimental results with the predictions of two competing hypotheses: infomax, which predicts that information conveyed about the entire signal range should be maximized, and selective coding, which predicts that “foreground” signals should be enhanced while “background” signals should be selectively suppressed. We test how adaptation changes the input–response curve when presenting signals with two or three peaks in their amplitude distributions, for which selective coding and infomax predict conflicting changes. By means of Bayesian data analysis, we quantify the shifts of the measured response curves and also find a slight reduction of their slopes. These decreases in slopes are smaller, and the absolute response thresholds are higher than those predicted by infomax. Most remarkably, and in contrast to the infomax principle, adaptation actually reduces the amount of encoded information when considering the whole range of input signals. The response curve changes are also not consistent with the selective coding hypothesis, because the amount of information conveyed about the loudest part of the signal does not increase as predicted but remains nearly constant. Less information is transmitted about signals with lower intensity

Cross-national mixed methods comparative case study of recovery-focused mental health care planning and coordination in acute inpatient mental health settings (COCAPP-A)

Background: Serious concerns have been identified in relation to care planning, patient involvement and consent to treatment in mental health wards, including for those patients detained under the Mental Health Act. Further evidence is needed to develop care planning interventions that embed dignity, recovery and participation for all people using inpatient mental health care. Design: We propose to undertake a cross-national comparative study of recovery-focused mental health care planning in inpatient settings. This two-phase exploratory mixed methods study will produce theory and empirical evidence to complement that developed in our current study of community mental health services to inform a future whole systems intervention study. The study is guided by a theoretical framework emphasising the connections between different 'levels' of organisation (macro/meso/micro). In phase 1 we study the macro-level through the comparative analysis of English and Welsh policy contexts. In phase 2 concurrent quantitative and qualitative data will be collected at 6 NHS Trust/Health Board case study sites (meso-level) and within each site, a single micro-level mental health ward will be selected to provide in-depth qualitative data related to care planning processes. Phase 1: We will extend our current meta-narrative mapping review (Wong et al 2013) of English and Welsh policies and the international literature on personalised recovery-oriented care planning and coordination in community settings to include inpatient settings. We will provide a review of evidence that is useful, rigorous and relevant for service providers and decision-makers and to inform Phase 2. Phase 2: We are employing a concurrent transformative mixed methods approach with embedded case studies (Creswell 2009: 215). We will conduct six in-depth meso-level case study investigations across contrasting NHS Trusts in England (n=4) and Local Health Boards in Wales (n=2), selected to reflect variety in geography and population and include a mix of rural, urban and inner city settings providing routine inpatient care. A large sample of service users (total n=300), inpatient staff (n=300) and informal carers (n=150) will be surveyed about perceptions of acute mental health care and care planning, recovery oriented practices, therapeutic relationships and empowerment using validated questionnaires. Documents and interviews with managers, consultant psychiatrists, ward staff and informal carers (n=60) will also be generated relating to local contexts, policies and practices. In each site we will also select a single inpatient ward and conduct a series of case studies embedded within each organisational case study, to explore care planning in detail. We will invite a sample of service users (total n=36) to participate in in-depth interviews about care planning and structured narrative reviews of their care plans; undertake a structured review of anonymised care plans for a further sample (n=60) of consecutively discharged patients; and conduct observation of care planning processes (n= 18). Framework method will be employed to integrate and compare textual and statistical summaries of qualitative and quantitative analyses within each case study site, informed by the theoretical framework focused on recovery and personalisation. Armed with our set of six within-case analyses we will then conduct a cross-case analysis to draw out key findings from across all sites

Contrast Adaptation Contributes to Contrast-Invariance of Orientation Tuning of Primate V1 Cells

BACKGROUND: Studies in rodents and carnivores have shown that orientation tuning width of single neurons does not change when stimulus contrast is modified. However, in these studies, stimuli were presented for a relatively long duration (e. g., 4 seconds), making it possible that contrast adaptation contributed to contrast-invariance of orientation tuning. Our first purpose was to determine, in marmoset area V1, whether orientation tuning is still contrast-invariant with the stimulation duration is comparable to that of a visual fixation. METHODOLOGY/PRINCIPAL FINDINGS: We performed extracellular recordings and examined orientation tuning of single-units using static sine-wave gratings that were flashed for 200 msec. Sixteen orientations and three contrast levels, representing low, medium and high values in the range of effective contrasts for each neuron, were randomly intermixed. Contrast adaptation being a slow phenomenon, cells did not have enough time to adapt to each contrast individually. With this stimulation protocol, we found that the tuning width obtained at intermediate contrast was reduced to 89% (median), and that at low contrast to 76%, of that obtained at high contrast. Therefore, when probed with briefly flashed stimuli, orientation tuning is not contrast-invariant in marmoset V1. Our second purpose was to determine whether contrast adaptation contributes to contrast-invariance of orientation tuning. Stationary gratings were presented, as previously, for 200 msec with randomly varying orientations, but the contrast was kept constant within stimulation blocks lasting >20 sec, allowing for adaptation to the single contrast in use. In these conditions, tuning widths obtained at low contrast were still significantly less than at high contrast (median 85%). However, tuning widths obtained with medium and high contrast stimuli no longer differed significantly. CONCLUSIONS/SIGNIFICANCE: Orientation tuning does not appear to be contrast-invariant when briefly flashed stimuli vary in both contrast and orientation, but contrast adaptation partially restores contrast-invariance of orientation tuning

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Philosophy Bernasconi-K of ohn the Social / A Response Sciences to Stueber How Not to Think about Rules and Rule Following

This article offers a critique of Karsten Stueber’s account of rule following as presented in his article “How to Think about Rules and Rule Following. ” The task Stueber sets himself is of defending the idea that human practices are bound and guided by rules (both causally and normatively) while avoiding the discredited “cognitive model of rule following. ” This article argues that Stueber’s proposal is unconvincing because it falls foul of the very problems it sets out to avoid. Stueber’s defense of rules as normative guides is shown to be either circular or burdened with an infinite regress, while his account of rules as causal determinants of our actions is shown to lapse back into the “cognitive model ” that he explicitly rejects