Neural activity of retinal ganglion cells under continuous, dynamically-modulated high frequency electrical stimulation

Objective. Current retinal prosthetics are limited in their ability to precisely control firing patterns of functionally distinct retinal ganglion cell (RGC) types. The aim of this study was to characterise RGC responses to continuous, kilohertz-frequency-varying stimulation to assess its utility in controlling RGC activity. Approach. We used in vitro patch-clamp experiments to assess electrically-evoked ON and OFF RGC responses to frequency-varying pulse train sequences. In each sequence, the stimulation amplitude was kept constant while the stimulation frequency (0.5-10 kHz) was changed every 40 ms, in either a linearly increasing, linearly decreasing or randomised manner. The stimulation amplitude across sequences was increased from 10 to 300 µA. Main results. We found that continuous stimulation without rest periods caused complex and irreproducible stimulus-response relationships, primarily due to strong stimulus-induced response adaptation and influence of the preceding stimulus frequency on the response to a subsequent stimulus. In addition, ON and OFF populations showed different sensitivities to continuous, frequency-varying pulse trains, with OFF cells generally exhibiting more dependency on frequency changes within a sequence. Finally, the ability to maintain spiking behaviour to continuous stimulation in RGCs significantly reduced over longer stimulation durations irrespective of the frequency order. Significance. This study represents an important step in advancing and understanding the utility of continuous frequency modulation in controlling functionally distinct RGCs. Our results indicate that continuous, kHz-frequency-varying stimulation sequences provide very limited control of RGC firing patterns due to inter-dependency between adjacent frequencies and generally, different RGC types do not display different frequency preferences under such stimulation conditions. For future stimulation strategies using kHz frequencies, careful consideration must be given to design appropriate pauses in stimulation, stimulation frequency order and the length of continuous stimulation duration

On the relations between historical epistemology and students’ conceptual developments in mathematics

There is an ongoing discussion within the research field of mathematics education regarding the utilization of the history of mathematics within mathematics education. In this paper we consider problems that may emerge when the historical epistemology of mathematics is paralleled to students’ conceptual developments in mathematics. We problematize this attempt to link the two fields on the basis of Grattan-Guinness’ distinction between “history” and “heritage”. We argue that when parallelism claims are made, history and heritage are often mixed up, which is problematic since historical mathematical definitions must be interpreted in its proper historical context and conceptual framework. Furthermore, we argue that cultural and local ideas vary at different time periods, influencing conceptual developments in different directions regardless of whether historical or individual developments are considered, and thus it may be problematic to uncritically assume a platonic perspective. Also, we have to take into consideration that an average student of today and great mathematicians of the past are at different cognitive levels

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans

Unresolved orthology and peculiar coding sequence properties of lamprey genes: the KCNA gene family as test case

Background:In understanding the evolutionary process of vertebrates, cyclostomes (hagfishes and lamprey) occupy crucial positions. Resolving molecular phylogenetic relationships of cyclostome genes with gnathostomes (jawed vertebrates) genes is indispensable in deciphering both the species tree and gene trees. However, molecular phylogenetic analyses, especially those including lamprey genes, have produced highly discordant results between gene families. To efficiently scrutinize this problem using partial genome assemblies of early vertebrates, we focused on the potassium voltage-gated channel, shaker-related (KCNA) family, whose members are mostly single-exon.Results:Seven sea lamprey KCNA genes as well as six elephant shark genes were identified, and their orthologies to bony vertebrate subgroups were assessed. In contrast to robustly supported orthology of the elephant shark genes to gnathostome subgroups, clear orthology of any sea lamprey gene could not be established. Notably, sea lamprey KCNA sequences displayed unique codon usage pattern and amino acid composition, probably associated with exceptionally high GC-content in their coding regions. This lamprey-specific property of coding sequences was also observed generally for genes outside this gene family.Conclusions:Our results suggest that secondary modifications of sequence properties unique to the lamprey lineage may be one of the factors preventing robust orthology assessments of lamprey genes, which deserves further genome-wide validation. The lamprey lineage-specific alteration of protein-coding sequence properties needs to be taken into consideration in tackling the key questions about early vertebrate evolution

The need of dermatologists, psychiatrists and psychologists joint care in psychodermatology

The mind-skin connection has been studied since the nineteenth century. The last 40 years have set the development of new research areas which allowed the clarifying of how these two dimensions interact. The diseases that involve skin and mind constitute the field of psychodermatology and require that specialists in dermatology, psychiatry and psychology together and integrated take part in it, since skin, nervous system and mind are simultaneously affected. This paper aims to expose how psychodermatoses are currently conceptualized and the need of integration of these three specialties for conveniently treating the patients

Free-Space distribution of entanglement and single photons over 144 km

Quantum Entanglement is the essence of quantum physics and inspires fundamental questions about the principles of nature. Moreover it is also the basis for emerging technologies of quantum information processing such as quantum cryptography, quantum teleportation and quantum computation. Bell's discovery, that correlations measured on entangled quantum systems are at variance with a local realistic picture led to a flurry of experiments confirming the quantum predictions. However, it is still experimentally undecided whether quantum entanglement can survive global distances, as predicted by quantum theory. Here we report the violation of the Clauser-Horne-Shimony-Holt (CHSH) inequality measured by two observers separated by 144 km between the Canary Islands of La Palma and Tenerife via an optical free-space link using the Optical Ground Station (OGS) of the European Space Agency (ESA). Furthermore we used the entangled pairs to generate a quantum cryptographic key under experimental conditions and constraints characteristic for a Space-to-ground experiment. The distance in our experiment exceeds all previous free-space experiments by more than one order of magnitude and exploits the limit for ground-based free-space communication; significantly longer distances can only be reached using air- or space-based platforms. The range achieved thereby demonstrates the feasibility of quantum communication in space, involving satellites or the International Space Station (ISS).Comment: 10 pages including 2 figures and 1 table, Corrected typo

Functional outcome in older adults with joint pain and comorbidity: design of a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Joint pain is a highly prevalent condition in the older population. Only a minority of the older adults consult the general practitioner for joint pain, and during consultation joint pain is often poorly recognized and treated, especially when other co-existing chronic conditions are involved. Therefore, older adults with joint pain and comorbidity may have a higher risk of poor functional outcome and decreased quality of life (QoL), and possibly need more attention in primary care. The main purpose of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to identify possible predictors of poor functional outcome. The study will also identify predictors of decreased QoL. The results will be used to develop prediction models for the early identification of subgroups at high risk of poor functional outcome and decreased QoL. This may contribute to better targeting of treatment and to more effective health care in this population.</p> <p>Methods/Design</p> <p>The study has been designed as a prospective cohort study, with measurements at baseline and after 6, 12 and 18 months. For the recruitment of 450 patients, 25 general practices will be approached. Patients are eligible for participation if they are 65 years or older, have at least two chronic conditions and report joint pain on most days. Data will be collected using various methods (i.e. questionnaires, physical tests, patient interviews and focus groups). We will measure different aspects of functioning (e.g. mobility, functional independence and participation) and QoL. Other measurements concern possible predictors of functioning and QoL (e.g. pain, co-existing chronic conditions, markers for frailty, physical performance, psychological factors, environmental factors and individual factors). Furthermore, health care utilization, health care needs and the meaning and impact of joint pain will be investigated from an older person's perspective.</p> <p>Discussion</p> <p>In this paper, we describe the protocol of a prospective cohort study in Dutch older adults with joint pain and comorbidity and discuss the potential strengths and limitations of the study.</p