Formulation and performance of variational integrators for rotating bodies

Variational integrators are obtained for two mechanical systems whose configuration spaces are, respectively, the rotation group and the unit sphere. In the first case, an integration algorithm is presented for Euler’s equations of the free rigid body, following the ideas of Marsden et al. (Nonlinearity 12:1647–1662, 1999). In the second example, a variational time integrator is formulated for the rigid dumbbell. Both methods are formulated directly on their nonlinear configuration spaces, without using Lagrange multipliers. They are one-step, second order methods which show exact conservation of a discrete angular momentum which is identified in each case. Numerical examples illustrate their properties and compare them with existing integrators of the literature

High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain

Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 µM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherin-positive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain

The detection and sensory perception of inspiratory resistive loads in people with chronic tetraplegia

This study investigated sensations of breathing following tetraplegia. Fifteen people with chronic tetraplegia and fifteen healthy able-bodied controls matched for age, sex, height, and weight participated. Sensations of breathing were quantified by determining the threshold for detecting an added resistance during inspiration. In a separate task, the perceived magnitudes of six suprathreshold resistive loads were determined with a modified Borg scale. The detection threshold of 0.34 cmH2O/L/s [standard deviation (SD) 0.14] in the tetraplegia group was higher than the 0.23 cmH2O/L/s (SD 0.10) threshold for able-bodied controls (P = 0.004). Both participant groups perceived larger loads to be more effortful, with the Borg effort rating increasing linearly with the peak inspiratory pressure generated at each load. The relationship between Borg effort rating and peak inspiratory pressure was steeper in participants with tetraplegia than in able-bodied controls (P = 0.001), but there was no difference when pressure was divided by maximal inspiratory pressure (P = 0.95). Despite a higher detection threshold, the findings suggest that the perceived magnitude of a suprathreshold inspiratory load is not impaired in chronic tetraplegia and that load magnitude perception is related to the maximal, and not absolute, inspiratory muscle force. NEW & NOTEWORTHY Sensations of breathing are thought to be impaired following chronic tetraplegia. The detection threshold for an added resistive load during inspiration was higher in people with tetraplegia than in healthy able-bodied participants. However, for inspiratory loads above the detection threshold, the perceived magnitude of a resistive load as a function of the peak inspiratory pressure was greater in tetraplegia. Load magnitude perception was comparable between participant groups when peak pressure was divided by maximal inspiratory pressure

The reliability of inspiratory resistive load magnitude and detection testing

Objectives: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. Design: Cohort of convenience. Setting: Respiratory physiology laboratory. Participants: Twenty healthy adults. Interventions: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome Measures: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. Results: ICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. Conclusions: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease

An evaluation of dexterity and cutaneous sensibility tests for use with medical gloves

© 2015 Institution of Mechanical Engineers.The ability of selected dexterity and cutaneous sensibility tests to measure the effect of medical glove properties (material, fit, and number of layers) on manual performance was analyzed. Manual performance testing of gloves to-date has focused on thicker gloves where the effects are more obvious. However, clinicians have reported dissatisfaction with some medical gloves and a perceived detriment to performance of new materials compared to latex. Three tests (Purdue Pegboard Test, Crawford Small Parts Dexterity Test, and Semmes-Weinstein Monofilaments) were performed by 18 subjects in five hand conditions (ungloved; best-fitting, loose-fitting and a double layer of latex examination gloves; best-fitting vinyl gloves). Tests were performed in the ungloved condition first, and the order of the gloved tests was randomized. Learning behavior was also measured. The Purdue test showed a significant effect of hand condition, but no differences between latex and vinyl. No significant effect of hand condition was found in the Crawford "Pins and Collars" test, but the "Screws" test showed promising discrimination between glove types. The Monofilaments test showed a significant effect of hand condition on cutaneous sensibility, particularly a reduction when "double-gloving," but no significant differences between glove types. Existing tests show some ability to measure the effect of gloves and their properties on manual performance but are not comprehensive and require further validation. In order to fully describe the effects of medical gloves on manual performance, further tests should be designed with greater resolution and that better replicate clinical manual tasks

Liver transplantation: Intraoperative changes in coagulation factors in 100 first transplants

Six intraoperative blood samples were obtained at intervals from each of 100 individuals undergoing their first liver transplants. The patients fell into the following diagnostic categories: postnecrotic cirrhosis 28, primary biliary cirrhosis 20, sclerosing cholangitis 19, miscellaneous diseases 14, carcinoma/neoplasia 12 and fulminant hepatitis 7. Coagulation factor values in the initial (baseline) blood samples varied by patient diagnosis. In general, all factor levels were reduced except factor VIII:C, which was increased to almost twice normal. The slight intraoperative changes in factors II, VII, IX, X, XI and XII suggested that a steady‐state relationship existed between depletion (consumption/bleeding) and repletion (transfusion, transit from extra‐ to intravascular space), even in the anhepatic state. In contrast, there were rapid and very significant falls in factor VIII and fibrinogen and a less pronounced decrease in factor V, all reaching their nadirs in early to mid‐Stage III. The cause of these coagulation changes appears to be activation of the fibrinolytic system. Copyright © 1989 American Association for the Study of Liver Disease

An integrative view of mammalian seasonal neuroendocrinology

This is the peer reviewed version of the following article: Dardente, H., Wood, S.H., Ebling, F. & Sáenz de Miera, C. (2019). An integrative view of mammalian seasonal neuroendocrinology. Journal of neuroendocrinology. Journal of Neuroendocrinology, 31(5), e12729, which has been published in final form at https://doi.org/10.1111/jne.12729. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Seasonal neuroendocrine cycles that govern annual changes in reproductive activity, energy metabolism and hair growth are almost ubiquitous in mammals that have evolved at temperate and polar latitudes. Changes in nocturnal melatonin secretion regulating gene expression in the pars tuberalis (PT) of the pituitary stalk are a critical common feature in seasonal mammals. The PT sends signal(s) to the pars distalis of the pituitary to regulate prolactin secretion and thus the annual moult cycle. The PT also signals in a retrograde manner via thyroid‐stimulating hormone to tanycytes, which line the ventral wall of the third ventricle in the hypothalamus. Tanycytes show seasonal plasticity in gene expression and play a pivotal role in regulating local thyroid hormone (TH) availability. Within the mediobasal hypothalamus, the cellular and molecular targets of TH remain elusive. However, two populations of hypothalamic neurones, which produce the RF‐amide neuropeptides kisspeptin and RFRP3 (RF‐amide related peptide 3), are plausible relays between TH and the gonadotrophin‐releasing hormone‐pituitary‐gonadal axis. By contrast, the ways by which TH also impinges on hypothalamic systems regulating energy intake and expenditure remain unknown. Here, we review the neuroendocrine underpinnings of seasonality and identify several areas that warrant further research

Atherosclerosis

Atherosclerosis, the formation of fibrofatty lesions in the artery wall, causes much morbidity and mortality worldwide, including most myocardial infarctions and many strokes, as well as disabling peripheral artery disease. Development of atherosclerotic lesions probably requires low-density lipoprotein, a particle that carries cholesterol through the blood. Other risk factors for atherosclerosis and its thrombotic complications include hypertension, cigarette smoking and diabetes mellitus. Increasing evidence also points to a role of the immune system, as emerging risk factors include inflammation and clonal haematopoiesis. Studies of the cell and molecular biology of atherogenesis have provided considerable insight into the mechanisms that link all these risk factors to atheroma development and the clinical manifestations of this disease. An array of diagnostic techniques, both invasive (such as selective coronary arteriography) and noninvasive (such as blood biomarkers, stress testing, CT and nuclear scanning), permit assessment of cardiovascular disease risk and targeting of therapies. An expanding armamentarium of therapies that can modify risk factors and confer clinical benefit is available; however, we face considerable challenge in providing equitable access to these treatments and in maximizing adherence. Yet, the clinical application of the fruits of research has advanced preventive strategies, enhanced clinical outcomes in affected individuals, and improved their quality of life. Rapidly accelerating knowledge and continued research promise to provide further progress in combating this common chronic disease

Approximation of the critical buckling factor for composite panels

This article is concerned with the approximation of the critical buckling factor for thin composite plates. A new method to improve the approximation of this critical factor is applied based on its behavior with respect to lamination parameters and loading conditions. This method allows accurate approximation of the critical buckling factor for non-orthotropic laminates under complex combined loadings (including shear loading). The influence of the stacking sequence and loading conditions is extensively studied as well as properties of the critical buckling factor behavior (e.g concavity over tensor D or out-of-plane lamination parameters). Moreover, the critical buckling factor is numerically shown to be piecewise linear for orthotropic laminates under combined loading whenever shear remains low and it is also shown to be piecewise continuous in the general case. Based on the numerically observed behavior, a new scheme for the approximation is applied that separates each buckling mode and builds linear, polynomial or rational regressions for each mode. Results of this approach and applications to structural optimization are presented