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Classical drug development is compromised by considerable clinical failure of promising drug candidates after decades of costly preclinical work. Failure can be because of previously unrecognized safety concerns or more commonly lack of clinical efficacy. Classical drug discovery and safety pharmacology programs rely heavily on well-established in vitro and preclinical animal models. The availability of human pluripotent stem cells and the possibility to direct them into any somatic cell type suggest that a paradigm shift in drug development may be possible and timely, with the opportunity to test safety and efficacy of candidate drugs on the human target cells and tissue. However, there is considerable uncertainty as to whether human models would only qualify as replacement for well-established tools or add substantially more information to the preclinical data package, to facilitate translation of more promising drug candidates into clinical practice. This chapter provides an overview of tissue-engineered macro-scale heart muscle models for applications in drug discovery and safety pharmacology.Sensorimotor delays dictate that humans act on outdated perceptual information. As a result, continuous manual tracking of an unpredictable target incurs significant response delays. Ku-0059436 However, no such delays are observed for repeating targets such as the sinusoids. Findings of this kind have led researchers to claim that the nervous system constructs predictive, probabilistic models of the world. However, a more parsimonious explanation is that visual perception of a moving target position is systematically biased by its velocity. The resultant extrapolated position could be compared with the cursor position and the difference canceled by negative feedback control, compensating sensorimotor delays. The current study tested whether a position extrapolation model fit human tracking of sinusoid (predictable) and pseudorandom (less predictable) targets better than the non-biased position control model, Twenty-eight participants tracked these targets and the two computational models were fit to the data at 60 fixed loop delay values (simulating sensorimotor delays). We observed that pseudorandom targets were tracked with a significantly greater phase delay than sinusoid targets. For sinusoid targets, the position extrapolation model simulated tracking results more accurately for loop delays longer than 120 ms, thereby confirming its ability to compensate for sensorimotor delays. However, for pseudorandom targets, this advantage arose only after 300 ms, indicating that velocity information is unlikely to be exploited in this way during the tracking of less predictable targets. We conclude that negative feedback control of position is a parsimonious model for tracking pseudorandom targets and that negative feedback control of extrapolated position is a parsimonious model for tracking sinusoidal targets.Several studies have shown that space immediately surrounding the body, or the peripersonal space is represented differently in the brain from the more distant extra-personal space. Moreover, the boundary of peripersonal space can be extended to space surrounding the tip of a tool held by the hand. However, it is not known if tools need to be connected to the body to modulate the peripersonal space. We used a line bisection task to investigate whether peripersonal space representation surrounds a virtual hand avatar that is disconnected from the body. Healthy participants conducted a line bisection task by responding with either a virtual hand avatar or a laser pointer. The to-be-bisected lines were presented either in peripersonal or extra-personal space. When the lines were placed in extra-personal space, the virtual hand avatar was presented near the line such that the hand avatar was far from participants and disconnected from their bodies. Results indicated a shift in the line bisection bias from the left to the right as the line presentation distance increased when using the laser pointer, whereas no shift in bias was observed when using the virtual hand avatar. This result indicates that objects resembling human hands presented even at a distance and disconnected from the body can be integrated into the peripersonal space, which suggests that peripersonal space representation is more flexible than previously reported.
The palmaris longus (PL) tendon present a high degree of variations; the commonest is its absence which could reach more than 40% in some populations. The PL tendon is highly relevant in hand reconstructive surgery; however, MRI variations of PL tendon have been exceptionally reported. To this, this study investigated PL tendon variations using MRI in a Lebanese population.
This is a retrospective study of distal forearm MRI examinations to evaluate the presence, anatomical variations and morphometric of PL tendon. The outcomes were set as overall frequency, gender-based and side-base frequencies, correlations between prevalence and gender/side, morphological variants, thickness, and width of PL tendon.
The sample comprised 335 patients including a total of 339 MRI scans. The PL was present in 221 wrists (65.2%), and bilaterally in only one (25%) out of the 4 bilateral cases. All PL were located using the Axial T1 views. Univariate and multivariate analyses showed no correlation with side, gender, or Tesla power. The only morphological variation was a reversed PL in 2 cases (0.6%). The mean width was 4.24 ± 1.2mm. The mean thickness was 2.75 ± 0.6mm.
As far as we know, this is the first study to report the total array of variations of PL tendon using MRI, and its prevalence in a Lebanese population. The mean width of PL tendon calculated with high quality MR imaging was found to be similar to that reported by cadaveric studies.
As far as we know, this is the first study to report the total array of variations of PL tendon using MRI, and its prevalence in a Lebanese population. The mean width of PL tendon calculated with high quality MR imaging was found to be similar to that reported by cadaveric studies.
Typically, the axillary arch is defined as a fleshy slip running from latissimus dorsi to the anterior aspect of the humerus. Phylogeny seems to give the most relevant and plausible explanation of this anatomical variant as a remnant of the panniculus carnosus. However, authors are not unanimous about its origin. We report herein the incidence of axillary arch in a series of 40 human female dissections and present an embryologic and a comparative study in three domestic mammals.
Forty formalin-preserved Caucasian human female cadavers, one rat (Rattus norvegicus), one rabbit (Oryctolagus cuniculus) and one pig (Sus scrofa domesticus) cadavers were dissected bilaterally. A comparative, analytical and a descriptive studies of serial human embryological sections were carried out.
We found an incidence of axillary arch of 2.5% (n = 1 subject of 40) in Humans. We found a panniculus carnosus inserted on the anterior aspect of the humerus only in the rat and the rabbit but not in the pig. The development of the latissimus dorsi takes place between Carnegie stage 16-23, but the embryological study failed to explain the genesis of the axillary arch variation.
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