Coordination of lower limb segments during obstacle clearance in healthy adults and pathological populations

Conformément au « planar law » de la coordination intersegmentaire, lorsque les angles d’élévation de la cuisse, de la jambe et du pied sont tracés pour un cycle de marche, ils ont tendance à créer une boucle qui s’oriente sur un plan spatial en 3-dimensions (3D). Le principal objectif de cette thèse a été d'utiliser des techniques d'analyse relatives à cette loi pour mieux comprendre comment le système nerveux central (SNC) coordonne et met en œuvre les ajustements locomoteurs anticipatoires (ALAs) pour le franchissement d’obstacle dans les populations saines et pathologiques. L’étude 1 a examiné les points généraux pour les ALAs normaux et l’étude 2 a relié les amplitudes du mouvement segmentaire au travail mécanique effectué par les muscles fléchisseurs de la hanche et du genou. Les études 3 et 4 ont déterminé comment des déficiences respectives de l’ataxie cérébelleuse autosomique récessive de type 1 (ARCA-1) et d'un accident vasculaire cérébral (AVC) peuvent avoir une incidence sur le contrôle locomoteur. Chez les adultes sains, le déphasage entre les segments adjacents se sont révélés être corrélé à des caractéristiques du plan formé par les angles d’élévation du segment, et ces différences de phase ont changé systématiquement avec l'augmentation de la hauteur de l'obstacle. Il a été proposé que le SNC ajuste un patron locomoteur de base pour les contraintes environnementales par la manipulation des différentes phases de l’angle d'élévation entre les segments adjacents ainsi que par l'amplitude de l’angle d'élévation. L’étude de suivi a déterminé que lorsque les obstacles les plus hauts étaient franchis, les décalages de phase de la cuisse pour la jambe d’attaque, et pour la jambe de l’autre membre ont augmenté. Le travail effectué par les muscles de la hanche et du genou a influencé l’élévation de la cuisse différemment pour les membres d’attaques et suivants et il a été conclu que ces muscles n'ont pas de rôles spécifiques pour l’élévation et la progression du membre inférieur lors de l’ALA. Au lieu de cela, ces puissances musculaires peuvent résulter du contrôle dynamique des angles d’élévation. Lorsque l'on observe la coordination chez les participants avec ARCA-1 et AVC les trajectoires des angles d'élévation du membre inférieur ont continué à s’orienter sur un plan spatial en 3D. Chez les participants avec ARCA-1, une plus grande différence de phase entre les segments de la cuisse et la jambe a suggéré d'être un mécanisme de contrôle lorsque ce groupe augmente volontairement le dégagement des orteils pour enjamber des obstacles. Chez les participants avec un précédent d’AVC, cette différence de phase a été plus grande dans le membre non parétique, ce qui a été interprété comme nécessaire pour élever le membre en compensation pour le mauvais appui du membre parétique. Les résultats de cette thèse suggèrent des mécanismes de contrôle d’élévation segmentaire pour la mise en œuvre d’ALAs et mettent en évidence les mécanismes de compensation volontaire d’un tel contrôle dans des populations pathologiques.According to the planar law of intersegmental coordination, when elevation angles of the thigh, shank, and foot are plotted for a gait cycle, they tend to create a loop which orients on a plane in 3-dimensional space. The main goal of this thesis was to use analysis techniques related to this law to gain a better understanding of how the central nervous system coordinates and implements anticipatory locomotor adjustments (ALAs) for stepping over obstacles in healthy and pathological populations. Study 1 examined general issues of normal ALAs, while study 2 related the timing and amplitude of segment motion with mechanical work by hip and knee flexor muscles. Studies 3 and 4, determined how impairments such as autosomal recessive cerebellar ataxia type-1 (ARCA-1) and a previous stroke respectively affect locomotor control. In healthy adults, phasing differences between adjacent segments were shown to be correlated to characteristics of the plane formed by the segment elevation angles and these phase differences changed systematically with increasing obstacle height. It was proposed that the CNS adjusts a basic locomotor pattern for environmental constraints by manipulating elevation angle phase differences between adjacent segments as well as elevation angle amplitudes. The follow-up study determined that as higher obstacles were cleared, leading limb thigh phase lead and trailing limb shank phase lag increased. The work done by the hip and knee flexor muscles influenced thigh elevation differently in the leading and trailing limbs and it was concluded that these muscles do not have simple specific roles in elevating and progressing the lower limb during locomotion. Instead, these muscle powers may result from elevation angle waveform control dynamics. When observing coordination in the ARCA-1 and stroke participants, plotted segmental elevation angle trajectories continued to covary on a plane. In the ARCA-1 participants, a larger phase difference between the thigh and shank segments was suggested to be a voluntary control mechanism to increase toe clearance over obstacles. In participants with a previous stroke, this phase difference was greater in the non-paretic limb which was interpreted as being necessary to elevate this limb in compensation for poor support by the paretic limb. The results of this thesis suggest mechanisms of segment elevation control to implement ALAs and highlights voluntary compensatory mechanisms in such control in pathological populations

Central Nervous System Control of Dynamic Stability during Locomotion in Complex Environments

A major function of the central nervous system (CNS) during locomotion is the ability to maintain dynamic stability during threats to balance. The CNS uses reactive, predictive, and anticipatory mechanisms in order to accomplish this. Previously, stability has been estimated using single measures. Since the entire body works as a system, dynamic stability should be examined by integrating kinematic, kinetic, and electromyographical measures of the whole body. This thesis examines three threats to stability (recovery from a frontal plane surface translation, stepping onto and walking on a compliant surface, and obstacle clearance on a compliant surface). These threats to stability would enable a full body stability analysis for reactive, predictive, and anticipatory CNS control mechanisms. From the results in this study, observing various biomechanical variables provides a more precise evaluation of dynamic stability and how it is achieved. Observations showed that different methods of increasing stability (eg. Lowering full body COM, increasing step width) were controlled by differing CNS mechanisms during a task. This provides evidence that a single measure cannot determine dynamic stability during a locomotion task and the body must be observed entirely to determine methods used in the maintenance of dynamic stability

Tissue-specific regulatory elements in mammalian promoters

Transcription factor-binding sites and the cis-regulatory modules they compose are central determinants of gene expression. We previously showed that binding site motifs and modules in proximal promoters can be used to predict a significant portion of mammalian tissue-specific transcription. Here, we report on a systematic analysis of promoters controlling tissue-specific expression in heart, kidney, liver, pancreas, skeletal muscle, testis and CD4 T cells, for both human and mouse. We integrated multiple sources of expression data to compile sets of transcripts with strong evidence for tissue-specific regulation. The analysis of the promoters corresponding to these sets produced a catalog of predicted tissue-specific motifs and modules, and cis-regulatory elements. Predicted regulatory interactions are supported by statistical evidence, and provide a foundation for targeted experiments that will improve our understanding of tissue-specific regulatory networks. In a broader context, methods used to construct the catalog provide a model for the analysis of genomic regions that regulate differentially expressed genes

Immature Spinal Locomotor Output in Children with Cerebral Palsy

Cappellini G, P. Ivanenko Y, Martino G, et al. Immature Spinal Locomotor Output in Children with Cerebral Palsy. Frontiers in Physiology. 2016;7:478

Predicting Group II pulmonary hypertension: diagnostic accuracy of the H2FPEF and OPTICS scores in Scotland

Objective: Group II pulmonary hypertension (PH) can be challenging to distinguish from Group I PH without proceeding to right heart catheterisation (RHC). The diagnostic accuracy of the H2FPEF and OPTICS scores was investigated in Scotland. Methods: Patients were included in the study if they were referred to the Scottish Pulmonary Vascular Unit between 2016 and 2020 and subsequently diagnosed with Group II PH or Group I PH which was either idiopathic, heritable or pulmonary veno-occlusive disease. The established cut offs for the H2FPEF and for the OPTICS scores were applied retrospectively to predict the presence of Group II PH. The diagnosis from the scores were compared with the MDT consensus diagnosis following RHC. Results: 107 patients with Group I PH and 86 patients with Group II PH were included. Retrospective application of the OPTICS score demonstrated that pretest scoring would detect 28% of cases with Group II PH yet at the cost of misdiagnosing 4% of patients with Group I as Group II PH (specificity 0.96). The H2FPEF score had a far greater sensitivity (0.70) yet reduced specificity (0.91), leading to misdiagnosis of 9% of Group I PH cases. Conclusion: While the specificity of these scores was high, the lack of perfect specificity limits their utility as it results in missed patients with Group I PH. As a consequence, they cannot replace RHC as the means of diagnosing the aetiology of PH in their current form. The scores may still be used to support clinical judgement or to indicate the advisability for further provocative testing at RHC

Induced photon correlations through the overlap of two four-wave mixing processes in integrated cavities

Induced photon correlations are directly demonstrated by exploring two coupled nonlinear processes in an integrated device. Using orthogonally polarized modes within an integrated microring cavity, phase matching of two different nonlinear four-wave mixing processes is achieved simultaneously, wherein both processes share one target frequency mode, while their other frequency modes differ. The overlap of these modes leads to the coupling of both nonlinear processes, producing photon correlations. The nature of this process is confirmed by means of time- and power-dependent photon correlation measurements. These findings are relevant to the fundamental understanding of spontaneous parametric effects as well as single-photon-induced processes, and their effect on optical quantum state generation and control

Arbitrary Phase Access for Stable Fiber Interferometers

Well-controlled yet practical systems that give access to interference effects are critical for established and new functionalities in ultrafast signal processing, quantum photonics, optical coherence characterization, etc. Optical fiber systems constitute a central platform for such technologies. However, harnessing optical interference in a versatile and stable manner remains technologically costly and challenging. Here, degrees of freedom native to optical fibers, i.e., polarization and frequency, are used to demonstrate an easily deployable technique for the retrieval and stabilization of the relative phase in fiber interferometric systems. The scheme gives access (without intricate device isolation) to <1.3 × 10−3 π rad error signal Allan deviation across 1 ms to 1.2 h integration times for all tested phases, ranging from 0 to 2π. More importantly, the phase-independence of this stability is shown across the full 2π range, granting access to arbitrary phase settings, central for, e.g., performing quantum projection measurements and coherent pulse recombination. Furthermore, the scheme is characterized with attenuated optical reference signals and single-photon detectors, and extended functionality is demonstrated through the use of pulsed reference signals (allowing time-multiplexing of both main and reference signals). Finally, the scheme is used to demonstrate radiofrequency-controlled interference of high-dimensional time-bin entangled states. © 2021 The Authors. Laser & Photonics Reviews published by Wiley-VCH Gmb

Undiagnosed osteoid osteoma of the spine presenting as painful scoliosis from adolescence to adulthood: a case report

Presented here is a case of a young woman, with an undiagnosed osteoid osteoma of the spine, which presented with painful scoliosis in adolescence and was treated by bracing until her accession to adulthood. A more thorough investigation, years after the initial one, revealed the tumor. Surgical excision and stabilization offered the long-awaited cure. Misdiagnosis resulted in intractable pain for years, deformity, the discomfort of brace therapy, and the frustration of a prolonged yet ineffective treatment

Generation and coherent control of pulsed quantum frequency combs

We present a method for the generation and coherent manipulation of pulsed quantum frequency combs. Until now, methods of preparing high-dimensional states on-chip in a practical way have remained elusive due to the increasing complexity of the quantum circuitry needed to prepare and process such states. Here, we outline how high-dimensional, frequency-bin entangled, two-photon states can be generated at a stable, high generation rate by using a nested-cavity, actively mode-locked excitation of a nonlinear micro-cavity. This technique is used to produce pulsed quantum frequency combs. Moreover, we present how the quantum states can be coherently manipulated using standard telecommunications components such as programmable filters and electro-optic modulators. In particular, we show in detail how to accomplish state characterization measurements such as density matrix reconstruction, coincidence detection, and single photon spectrum determination. The presented methods form an accessible, reconfigurable, and scalable foundation for complex high-dimensional state preparation and manipulation protocols in the frequency domain

Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp3-rich library

The application of a tandem condensation/cyclisation/[3+2]-cycloaddition/elimination reaction gives an sp3-rich tricyclic pyrazoline scaffold with two ethyl esters in a single step from a simple linear starting material. The successive hydrolysis and cyclisation (with Boc anhydride) of these 3-dimensional architectures, generates unprecedented 16-membered macrocyclic bisanhydrides (characterised by XRD). Selective amidations could then be achieved by ring opening with a primary amine followed by HATU-promoted amide coupling to yield an sp3-rich natural product-like library