Force measurement during spinal mobilisation

PhDSpinal mobilisation or manipulation techniques are frequently used by physiotherapists in the treatment of musculoskeletal disorders. Despite the reliance on these techniques in clinical practice, there is little scientific evidence to substantiate their use. A standard mobilisation couch was instrumented to enable measurement of the forces applied to the trunk during mobilisation of the lumbar spine. Six load cells were incorporated into the couch frame and linked to a personal computer to facilitate data collection. The couch allowed the assessment of the magnitude of the mobilisation force, its direction and the variation in applied load over time. The system was found to be reliable and sensitive over the range of forces applied during mobilisation. The system was used to collect data from a sample of 30 experienced therapists to evaluate repeatability and reproducibility during the application of four grades of a posteroanterior mobilisation and an End Feel, on the third lumbar vertebra. Whilst some therapists demonstrated considerable variation in the forces applied both within one measurement session and over a two week period, others were found to be relatively consistent. The range of forces used by different therapists when performing the same technique was substantial ranging between 63 N and 347 N for a Grade IV mobilisation. A study was carried out involving 26 young healthy subjects, to determine the characteristics of a mobilisation force applied to an asymptomatic spine. A further study was undertaken involving a clinical sample of 16 patients, aged between 47- 64 years, to evaluate the effect of age related degenerative changes of the lumbar spine on the application of these techniques. The magnitude of the mobilisation force was found to be similar for the healthy and the patient groups with median forces of 175 N and 171 N during a Grade IV procedure, respectively. However, the forces applied to the patient group exhibited a statistically significantly smaller amplitude and higher frequency of oscillation than the healthy group for the same procedure (p < 0.01). Such measurements are essential for the assessment of the efficacy of these techniques in clinical practice.Chartered Society of Physiotherap

Measuring properties of primordial black hole mergers at cosmological distances: effect of higher order modes in gravitational waves

Primordial black holes (PBHs) may form from the collapse of matter overdensities shortly after the Big Bang. One may identify their existence by observing gravitational wave (GW) emissions from merging PBH binaries at high redshifts $z\gtrsim 30$, where astrophysical binary black holes (BBHs) are unlikely to merge. The next-generation ground-based GW detectors, Cosmic Explorer and Einstein Telescope, will be able to observe BBHs with total masses of $\mathcal{O}(10-100)~M_{\odot}$ at such redshifts. This paper serves as a companion paper of arXiv:2108.07276, focusing on the effect of higher-order modes (HoMs) in the waveform modeling, which may be detectable for these high redshift BBHs, on the estimation of source parameters. We perform Bayesian parameter estimation to obtain the measurement uncertainties with and without HoM modeling in the waveform for sources with different total masses, mass ratios, orbital inclinations and redshifts observed by a network of next-generation GW detectors. We show that including HoMs in the waveform model reduces the uncertainties of redshifts and masses by up to a factor of two, depending on the exact source parameters. We then discuss the implications for identifying PBHs with the improved single-event measurements, and expand the investigation of the model dependence of the relative abundance between the BBH mergers originating from the first stars and the primordial BBH mergers as shown in arXiv:2108.07276.Comment: 11 pages, 11 figure

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

On the single-event-based identification of primordial black hole mergers at cosmological distances

The existence of primordial black holes (PBHs), which may form from the collapse of matter overdensities shortly after the Big Bang, is still under debate. Among the potential signatures of PBHs are gravitational waves (GWs) emitted from binary black hole (BBH) mergers at redshifts z ≳ 30, where the formation of astrophysical black holes is unlikely. Future ground-based GW detectors, the Cosmic Explorer and Einstein Telescope, will be able to observe equal-mass BBH mergers with total mass of (10–100)M⊙ at such distances. In this work, we investigate whether the redshift measurement of a single BBH source can be precise enough to establish its primordial origin. We simulate BBHs of different masses, mass ratios and orbital orientations. We show that for BBHs with total masses between 20 M ⊙ and 40 M ⊙ merging at z ≥ 40, one can infer z > 30 at up to 97% credibility, with a network of one Einstein Telescope, one 40 km Cosmic Explorer in the US, and one 20 km Cosmic Explorer in Australia. This number reduces to 94% with a smaller network made of one Einstein Telescope and one 40 km Cosmic Explorer in the US. We also analyze how the measurement depends on the Bayesian priors used in the analysis and verify that priors that strongly favor the wrong model yield smaller Bayesian evidences

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Science with the Einstein Telescope: a comparison of different designs

The Einstein Telescope (ET), the European project for a third-generation gravitational-wave detector, has a reference configuration based on a triangular shape consisting of three nested detectors with 10 km arms, where in each arm there is a `xylophone' configuration made of an interferometer tuned toward high frequencies, and an interferometer tuned toward low frequencies and working at cryogenic temperature. Here, we examine the scientific perspectives under possible variations of this reference design. We perform a detailed evaluation of the science case for a single triangular geometry observatory, and we compare it with the results obtained for a network of two L-shaped detectors (either parallel or misaligned) located in Europe, considering different choices of arm-length for both the triangle and the 2L geometries. We also study how the science output changes in the absence of the low-frequency instrument, both for the triangle and the 2L configurations. We examine a broad class of simple `metrics' that quantify the science output, related to compact binary coalescences, multi-messenger astronomy and stochastic backgrounds, and we then examine the impact of different detector designs on a more specific set of scientific objectives.Comment: 197 pages, 72 figure

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe