Carotid-femoral pulse wave velocity estimated by an ultrasound system

To date, regional aortic stiffness can be evaluated by the reference tonometric technique via the pulse wave velocity (PWV) measured in two points: the carotid and the femoral arteries. Based on a similar intersecting tangent algorithm, we have developed a new method for the determination of carotid-femoral PWV using a high-resolution echo tracking ultrasound system. Herein, PWV can be computed from the measurement of the transit time between the foot of the carotid diameter waveform and the foot of the femoral diameter waveform. The study was carried out on 50 consecutive patients at rest (29 men, mean age 30 ± 18 yrs) recruited on the occasion of a vascular screening for atherosclerosis. Carotid-femoral PWV was determined by a trained operator using a tonometric technique, (PWVpp, PulsePen, Italy), and an echotracking ultrasound system, (PWVus, e-tracking Alpha 10, Aloka, Japan). Relationship between PWVpp and PWVus was evaluated by linear regression. A Pearson’s correlation coefficient of r=0.95 was found between both variables (95% confidence interval 0.90-0.99; P<0.0001; PWVus= 0,91*PWVpp+0.44). The Bland–Altman plot comparing PWVpp and PWVus showed a systematic offset of -0.07 m.s-1 with a limit of agreement from -1,33 to 1,19 m.s-1. Our results show an excellent and significant correlation between both techniques which confirms that ultrasound system can provide a reliable estimate of the regional aortic stiffness like the tonometric technique does. Additional studies are now needed to show the simplicity of the measurement using ultrasound system while maintaining reliability even in overweight patients

Genetic evidence that SOST inhibits WNT signaling in the limb

AbstractSOST is a negative regulator of bone formation, and mutations in human SOST are responsible for sclerosteosis. In addition to high bone mass, sclerosteosis patients occasionally display hand defects, suggesting that SOST may function embryonically. Here we report that overexpression of SOST leads to loss of posterior structures of the zeugopod and autopod by perturbing anterior–posterior and proximal–distal signaling centers in the developing limb. Mutant mice that overexpress SOST in combination with Grem1 and Lrp6 mutations display more severe limb defects than single mutants alone, while Sost−/− significantly rescues the Lrp6−/− skeletal phenotype, signifying that SOST gain-of-function impairs limb patterning by inhibiting the WNT signaling through LRP5/6

Cannibalism as a life boat mechanism

Under certain conditions a cannibalistic population can survive when food for the adults is too scarce to support a non-cannibalistic population. Cannibalism can have this lifeboat effect if (i) the juveniles feed on a resource inaccessible to the adults; and (ii) the adults are cannibalistic and thus incorporate indirectly the inaccessible resource. Using a simple model we conclude that the mechanism works when, at low population densities, the average yield, in terms of new offspring, due to the energy provided by one cannibalized juvenile is larger than one

Rigidité artérielle mesurée par pOpmètre® chez les patients à risque cardiovasculaire, lien aux plaques d’athérome carotidien

PURPOSE: Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors. METHODS: In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system. RESULTS: No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P<0.002) with a larger intimae media thickness (0.69 ± 0.02 versus 0.63 ± 0.01 mm, P<0.004), a higher AoStiff (10.4 ± 0.7 versus 8.2 ± 0.5m/s, P<0.02), and PWVtf (14.3 ± 1.0 versus 10.7 ± 0.7 m/s, P<0.004) and a shorter Dt-f (57.9 ± 5.1 versus 73.5 ± 3.5 ms, P<0.01). PWVtf (r(2)=0.49, P<0.0001) and Dt-f (r(2)=0.54, P<0.0001) correlated with age. A significant difference in pOpscore(®) index was observed between both groups (1.51 ± 0.3 versus 1.41 ± 0.2, P<0.006). CONCLUSION: Our results show a significant arterial stiffness indices measured by pOpmetre(®) in patients with and without carotid plaques

Young children’s impressionable use of teleology: the influence of question wording and questioned topic on teleological explanations for natural phenomena

There is a significant body of research on children's preconceptions concerning scientific concepts and the impact this has upon their science education. One active issue concerns the extent to which young children's explanations for the existence of natural kinds rely on a teleological rationale: for example, rain is for watering the grass, or tigers’ stripes are for camouflage. It has been argued that this teleological tendency hampers children's ability to learn about causality in the natural world. This paper investigates two factors (question wording and topic) which it is argued have led to a misestimation of children's teleological tendencies within the area natural phenomena: i.e., those that are time-constrained, natural events or process such as snow, clouds or night. Sixty-six (5- to 8-years-old) children took part in a repeated-measures experiment, answering both open- and leading-questions across 10 topics of natural phenomena. The findings indicate that children's teleological reasoning may have been overestimated as open question forms significantly reduced their tendency to answer teleologically. Moreover, the concept of teleology is more nuanced than often suggested. Consequently, young children may be more able to learn about causal explanations for the existence of natural phenomena than the literature implies

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses

Control-based continuation of nonlinear structures using adaptive filtering

Control-Based Continuation uses feedback control to follow stable and unstable branches of periodic orbits of a nonlinear system without the need for advanced post-processing of experimental data. CBC relies on an iterative scheme to modify the harmonic content of the control reference and obtain a non-invasive control signal. This scheme currently requires to wait for the experiment to settle down to steady-state and hence runs offline (i.e. at a much lower frequency than the feedback controller). This paper proposes to replace this conventional iterative scheme by adaptive filters. Adaptive filters can directly synthesize either the excitation or the control reference adequately and can operate online (i.e. at the same frequency as the feedback controller). This novel approach is found to significantly accelerate convergence to non-invasive steady-state responses to the extend that the structure response can be characterized in a nearly-continuous amplitude sweep. Furthermore, the stability of the controller does not appear to be affected

Study of the Stabilization to the Nanometer Level of Mechanical Vibrations of the CLIC Main Beam

Original publication available at http://www.jacow.org/International audienceTo reach the design luminosity of CLIC, the movements of the quadrupoles should be limited to the nanometre level in order to limit the beam size and emittance growth. Below 1 Hz, the movements of the main beam quadrupoles will be corrected by a beambased feedback. But above 1 Hz, the quadrupoles should be mechanically stabilized. A collaboration effort is ongoing between several institutes to study the feasibility of the "nanostabilization" of the CLIC quadrupoles. The study described in this paper covers the characterization of independent measuring techniques including optical methods to detect nanometre sized displacements and analyze the vibrations. Actuators and feedback algorithms for sub-nanometre movements of magnets with a mass of more than 400 kg are being developed and tested. Input is given to the design of the quadrupole magnets, the supports and alignment system in order to limit the amplification of the vibration sources at resonant frequencies. A full scale mock-up integrating all these features is presently under design. Finally, a series of experiments in accelerator environments should demonstrate the feasibility of the nanometre stabilization