Why Neurons Are Not the Right Level of Abstraction for Implementing Cognition

International audienceThe cortex accounts for 70% of the brain volume. The human cortex is made of micro-columns, arrangements of 110 cortical neurons (Mountcastle), grouped in by the thousand in so-called macro-colums (or columns) which belong to the same functional unit as exemplified by Nobel laureates Hubel and Wiesel with the orientation columns of the primary visual cortex. The cortical column activity does not exhibit the limitations of single neurons: activation can be sustained for very long periods (sec.) instead of been transient and subject to fatigue. Therefore, the cortical column has been proposed as the building block of cognition by several researchers, but to not effect – since explanations about how the cognition works at the column level were missing. Thanks to the Theory of neuronal Cognition, it is no more the case. The cortex functionality is cut into small areas: the cortical maps. Today, about 80 cortical maps are known in the primary and secondary cortex [1]. These maps form a hierarchical organization. A cortical map is a functional structure encompassing several thousands of cortical columns. The function of such maps (also known as Kohonen maps) is to build topographic (i.e., organized and localized) representations of the input stimulii (events). This organization is such that similar inputs activate either the same cortical column or neighboring columns. Also, the more frequent the stimulus, the greater the number of cortical columns involved. Each map acts as a novelty detector and a filter. Events are reported as patterns of activations on various maps, each map specialized in a specific " dimension ". Spatial and temporal coordinates of events are linked to activations within the hippo-campus and define de facto the episodic memory. Learning is achieved at neuronal level using the famous Hebb's law: " Neurons active in the same time frame window reinforce their connections ". This rule does not respect " causality ". This, plus the fact that there is at least as much feedback connections as there are feed-forward ones, explain why a high level cortical activation generates a low level cortical pattern of activations – the same one that would trigger this high level activity. Therefore, our opinion is that the true building block of the cognition is a set of feed-forward and feedback connections between at least two maps, each map a novelty detector

Optimizing Accessibility of Wireless Emergency Alerts: 2015 Survey Findings

The Wireless Emergency Alert (WEA) system is a free, opt-out, national emergency alerting service that was deployed in 2012 as one component of the Integrated Public Alert and Warning Systems (IPAWS). Since 2012 over 10,000 WEA messages have been transmitted to mobile phones in the U.S. In 2015, a national online survey on WEAs (2015 WEA Survey) was conducted to understand the effectiveness of WEA messages for people with disabilities. The survey collected data on availability, awareness and accessibility of WEA messages, as well as actions taken by the recipient upon receipt. The survey also takes into consideration the type of mobile device used by the respondents. Project researchers hypothesized that greater awareness and exposure to WEA alerts would increase trust and appropriateness of individual responses to alerts. The analysis of the survey data supports the hypothesis. The 2015 WEA national online survey results provided policy and practice insights to improve the intended impact of WEA messages for people with disabilities

Development of a core measurement set for research in degenerative cervical myelopathy: a study protocol (AO Spine RECODE-DCM CMS)

INTRODUCTION Progress in degenerative cervical myelopathy (DCM) is hindered by inconsistent measurement and reporting. This impedes data aggregation and outcome comparison across studies. This limitation can be reversed by developing a core measurement set (CMS) for DCM research. Previously, the AO Spine Research Objectives and Common Data Elements for DCM (AO Spine RECODE-DCM) defined 'what' should be measured in DCM: the next step of this initiative is to determine 'how' to measure these features. This protocol outlines the steps necessary for the development of a CMS for DCM research and audit. METHODS AND ANALYSIS The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials and the Consensus-based Standards for the selection of health Measurement Instruments. The process involves five phases. In phase 1, the steering committee agreed on the constructs to be measured by sourcing consensus definitions from patients, professionals and the literature. In phases 2 and 3, systematic reviews were conducted to identify tools for each construct and aggregate their evidence. Constructs with and without tools were identified, and scoping reviews were conducted for constructs without tools. Evidence on measurement properties, as well as on timing of assessments, are currently being aggregated. These will be presented in phase 4: a consensus meeting where a multi-disciplinary panel of experts will select the instruments that will form the CMS. Following selection, guidance on the implementation of the CMS will be developed and disseminated (phase 5). A preliminary CMS review scheduled at 4 years from release. ETHICS AND DISSEMINATION Ethical approval was obtained from the University of Cambridge (HBREC2019.14). Dissemination strategies will include peer-reviewed scientific publications; conference presentations; podcasts; the identification of AO Spine RECODE-DCM ambassadors; and engagement with relevant journals, funders and the DCM community

HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants

The resolution of genome-wide association studies (GWAS) is limited by the linkage disequilibrium (LD) structure of the population being studied. Selecting the most likely causal variants within an LD block is relatively straightforward within coding sequence, but is more difficult when all variants are intergenic. Predicting functional non-coding sequence has been recently facilitated by the availability of conservation and epigenomic information. We present HaploReg, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants. Using LD information from the 1000 Genomes Project, linked SNPs and small indels can be visualized along with their predicted chromatin state in nine cell types, conservation across mammals and their effect on regulatory motifs. Sets of SNPs, such as those resulting from GWAS, are analyzed for an enrichment of cell type-specific enhancers. HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg.National Institutes of Health (U.S.) (R01-HG004037)National Institutes of Health (U.S.) (RC1-HG005334)National Science Foundation (U.S.) (HG005334

Stochastic modelling and prediction of fatigue crack propagation using piecewise-deterministic Markov processes

Fatigue crack propagation is a stochastic phenomenon due to the inherent uncertainties originating from material properties, environmental conditions and cyclic mechanical loads. Stochastic processes offer thus an appropriate framework for modelling and predicting crack propagation. In this paper, the fatigue crack growth is modelled and predicted by a piecewise-deterministic Markov process associated with deterministic crack laws. First, a regime-switching model is used to express the transition between Paris' regime and rapid propagation which occurs before failure. Both regimes of propagation are governed by a deterministic equation whose parameters are randomly selected in a finite state space. This one has been adjusted from real data available in the literature. The crack growth behaviour is well-captured and the transition between both regimes is well-estimated by a critical stress intensity factor range. The second purpose of our investigation deals with the prediction of the fatigue crack path and its variability based on measurements taken at the beginning of the propagation. The results show that our method based on this class of stochastic models associated with an updating method provides a reliable prediction and can be an efficient tool for safety analysis of structures in a large variety of engineering applications. In addition, the proposed strategy requires only few information to be effective and is not time-consuming

Efficient and accurate P-value computation for Position Weight Matrices

<p>Abstract</p> <p>Background</p> <p>Position Weight Matrices (PWMs) are probabilistic representations of signals in sequences. They are widely used to model approximate patterns in DNA or in protein sequences. The usage of PWMs needs as a prerequisite to knowing the statistical significance of a word according to its score. This is done by defining the P-value of a score, which is the probability that the background model can achieve a score larger than or equal to the observed value. This gives rise to the following problem: Given a P-value, find the corresponding score threshold. Existing methods rely on dynamic programming or probability generating functions. For many examples of PWMs, they fail to give accurate results in a reasonable amount of time.</p> <p>Results</p> <p>The contribution of this paper is two fold. First, we study the theoretical complexity of the problem, and we prove that it is NP-hard. Then, we describe a novel algorithm that solves the P-value problem efficiently. The main idea is to use a series of discretized score distributions that improves the final result step by step until some convergence criterion is met. Moreover, the algorithm is capable of calculating the exact P-value without any error, even for matrices with non-integer coefficient values. The same approach is also used to devise an accurate algorithm for the reverse problem: finding the P-value for a given score. Both methods are implemented in a software called TFM-PVALUE, that is freely available.</p> <p>Conclusion</p> <p>We have tested TFM-PVALUE on a large set of PWMs representing transcription factor binding sites. Experimental results show that it achieves better performance in terms of computational time and precision than existing tools.</p

On the structure of codimension 1 foliations with pseudoeffective conormal bundle.

International audienceLet $X$ a projective manifold equipped with a codimension $1$ (maybe singular) distribution whose conormal sheaf is assumed to be pseudoeffective. By a theorem of Jean-Pierre Demailly, this distribution is actually integrable and thus defines a codimension $1$ holomorphic foliation \F. We aim at describing the structure of such a foliation, especially in the non abundant case: It turns out that \F is the pull-back of one of the "canonical foliations" on a Hilbert modular variety. This result remains valid for ''logarithmic foliated pairs''

Hosting an Educational Careers Day Within the Virtual Paradigm: The Neurology and Neurosurgery Interest Group Experience.

INTRODUCTION:  To explore our experience of hosting the 10th Annual Neurology and Neurosurgery Interest Group-Society of British Neurological Surgeons (NANSIG-SBNS) Neurosurgery Careers Day, held virtually for the first time. METHODS:  Reflective feedback and review of an international, virtual neurosurgery careers day. The authors reflect on the logistics of organizing the event, and the pre- and post-event feedback provided by delegates. Recommendations have been made on how to successfully host a virtual event. The key themes that permeated the event have been outlined and discussed in the context of the feedback received. RESULTS:  The event was attended by 231 delegates from 20 countries worldwide. Knowledge of neurosurgery as a career and the application process increased after attending the careers day (4.27/5 to 4.51/5, p=0.003 and 3.12/5 to 4.31/5, p<0.001 respectively). The key themes identified from the event include attendance, networking, and education. Qualitative feedback was positive and indicated a positive perception of the careers day. CONCLUSIONS:  The future of educational events is unclear, and a hybrid approach is recommended to retain the benefits of the online space when in-person events eventually return