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

Metric gravity theories and cosmology:II. Stability of a ground state in f(R) theories

A fundamental criterion of viability of any gravity theory is existence of a stable ground-state solution being either Minkowski, dS or AdS space. Stability of the ground state is independent of which frame is physical. In general, a given theory has multiple ground states and splits into independent physical sectors. All metric gravity theories with the Lagrangian being a function of Ricci tensor are dynamically equivalent to Einstein gravity with a source and this allows us to study the stability problem using methods developed in GR. We apply these methods to f(R) theories. As is shown in 13 cases of Lagrangians the stability criterion works simply and effectively whenever the curvature of the ground state is determined. An infinite number of gravity theories have a stable ground state and further viability criteria are necessary.Comment: A modified and expanded version of a second part of the paper which previously appeared as gr-qc/0702097v1. The first, modified part is now published as gr-qc/0702097v2 and as a separate paper in Class. Qu. Grav. The present paper matches the published versio

Beyond Hebb: Exclusive-OR and Biological Learning

A learning algorithm for multilayer neural networks based on biologically plausible mechanisms is studied. Motivated by findings in experimental neurobiology, we consider synaptic averaging in the induction of plasticity changes, which happen on a slower time scale than firing dynamics. This mechanism is shown to enable learning of the exclusive-OR (XOR) problem without the aid of error back-propagation, as well as to increase robustness of learning in the presence of noise.Comment: 4 pages RevTeX, 2 figures PostScript, revised versio

The electromagnetic Christodoulou memory effect and its application to neutron star binary mergers

Gravitational waves are predicted by the general theory of relativity. It has been shown that gravitational waves have a nonlinear memory, displacing test masses permanently. This is called the Christodoulou memory. We proved that the electromagnetic field contributes at highest order to the nonlinear memory effect of gravitational waves, enlarging the permanent displacement of test masses. In experiments like LISA or LIGO which measure distances of test masses, the Christodoulou memory will manifest itself as a permanent displacement of these objects. It has been suggested to detect the Christodoulou memory effect using radio telescopes investigating small changes in pulsar’s pulse arrival times. The latter experiments are based on present-day technology and measure changes in frequency. In the present paper, we study the electromagnetic Christodoulou memory effect and compute it for binary neutron star mergers. These are typical sources of gravitational radiation. During these processes, not only mass and momenta are radiated away in form of gravitational waves, but also very strong magnetic fields are produced and radiated away. Moreover, a large portion of the energy is carried away by neutrinos. We give constraints on the conditions, where the energy transported by electromagnetic radiation is of similar or slightly higher order than the energy radiated in gravitational waves or in form of neutrinos. We find that for coalescing neutron stars, large magnetic fields magnify the Christodoulou memory as long as the gaseous environment is sufficiently rarefied. Thus the observed effect on test masses of a laser interferometer gravitational wave detector will be enlarged by the contribution of the electromagnetic field. Therefore, the present results are important for the planned experiments. Looking at the null asymptotics of spacetimes, which are solutions of the Einstein–Maxwell equations, we derive the electromagnetic Christodoulou memory effect. We obtain an exact solution of the full nonlinear problem, no approximations were used. Moreover, our results allow to answer astrophysical questions, as the knowledge about the amount of energy radiated away in a neutron star binary merger enables us to gain information about the source of the gravitational waves.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98597/1/0264-9381_29_21_215003.pd

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

TMS-EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (�50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at�100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at �1, �2, �3, and �5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the�1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABRagonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of �1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia

The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex

Measuring the brain's response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers unique insights into the cortical circuits activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (NMDA receptor antagonist) or placebo across two sessions in a double-blinded pseudo-randomised crossover design. At baseline, there were amplitude differences between PFC and PAR TEPs across a wide time range (15-250 ms), however the signals were correlated after ~80 ms, suggesting early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. Early TEP peaks were not reliably altered following dextromethorphan compared to placebo, although findings were less clear for later peaks, and low frequency resting oscillations were reduced in power. Our findings suggest that early TEP peaks (<80 ms) from PFC and PAR reflect stimulation site specific activity that is largely insensitive to changes in NMDA receptor-mediated neurotransmission.Nigel C. Rogasch, Carl Zipser, Ghazaleh Darmani, Tuomas P. Mutanen, Mana Biabani, Christoph Zrenner, Debora Desideri, Paolo Belardinelli, Florian Müller-Dahlhaus, Ulf Zieman

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)

Establishing Diagnostic Criteria for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 3].

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process. METHODS: Literature review summarising current evidence of establishing diagnostic criteria for DCM. RESULTS: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM. CONCLUSION: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities

Establishing Diagnostic Criteria for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 3].

STUDY DESIGN: Narrative review. OBJECTIVES: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process. METHODS: Literature review summarising current evidence of establishing diagnostic criteria for DCM. RESULTS: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. Therefore, making a prompt diagnosis of DCM in order to facilitate early surgical intervention is a clinical priority in DCM. CONCLUSION: There are often extensive delays in the diagnosis of DCM. Presently, no single set of diagnostic criteria exists for DCM, making it challenging for clinicians to make the diagnosis. Earlier diagnosis and subsequent specialist referral could lead to improved patient outcomes using existing treatment modalities