Heterosexual interactions of pairs of laboratory-housed stumptail macaques (Macaca arctoides) under continuous observation with closed-circuit video recording

Female-male interaction of heterosexual pairs of stumptail macaques, housed together continuously, was studied 24 hr per day using closed-circuit video recording. Two pairs were studied for approximately 2 months each. Although no generalizations can be made from such a small sample, no aspect of behavioral interaction varied significantly with the stage of the menstrual cycle of the female partner. Copulation occurred regularly but only during the daylight hours. Both pairs showed several peak ejaculation days (5-21 ejaculations/day), which were distributed throughout the entire menstrual cycle. In general, the highest number of ejaculations was observed to occur when the animals were put together either for the first time or following a separation of a few days. In one pair the female became pregnant, and from the fifth week of pregnancy onward there was a gradual increase in male aggression, coinciding with a decrease in male sexual and grooming behavior. In a second study eight different pairs were observed during the first day together and male copulatory behavior was studied. Two patterns of copulatory behavior could be discerned: pairs displaying a high number of ejaculations (19-38) and pairs displaying a low number of ejaculations (4-8). With regard to the interejaculatory interval (IEI), the male stumptail appeared to be unique. In contrast to what has been reported for other mammals, i.e., a steady increase in IEI with subsequent ejaculations, the stumptail showed increasing IEIs only during the first three to four, as well as between the last, ejaculations; in between, the IEI remained relatively constant. The maximum number of consecutive ejaculations observed was 38, displayed during a 10-hr time period (mean (± SEM)IEI, 12.9 ± 3.5 min)

Standardized ultrasound evaluation of carotid stenosis for clinical trials: University of Washington Ultrasound Reading Center

<p>Abstract</p> <p>Introduction</p> <p>Serial monitoring of patients participating in clinical trials of carotid artery therapy requires noninvasive precision methods that are inexpensive, safe and widely available. Noninvasive ultrasonic duplex Doppler velocimetry provides a precision method that can be used for recruitment qualification, pre-treatment classification and post treatment surveillance for remodeling and restenosis. The University of Washington Ultrasound Reading Center (UWURC) provides a uniform examination protocol and interpretation of duplex Doppler velocity measurements.</p> <p>Methods</p> <p>Doppler waveforms from 6 locations along the common carotid and internal carotid artery path to the brain plus the external carotid and vertebral arteries on each side using a Doppler examination angle of 60 degrees are evaluated. The UWURC verifies all measurements against the images and waveforms for the database, which includes pre-procedure, post-procedure and annual follow-up examinations. Doppler angle alignment errors greater than 3 degrees and Doppler velocity measurement errors greater than 0.05 m/s are corrected.</p> <p>Results</p> <p>Angle adjusted Doppler velocity measurements produce higher values when higher Doppler examination angles are used. The definition of peak systolic velocity varies between examiners when spectral broadening due to turbulence is present. Examples of measurements are shown.</p> <p>Discussion</p> <p>Although ultrasonic duplex Doppler methods are widely used in carotid artery diagnosis, there is disagreement about how the examinations should be performed and how the results should be validated. In clinical trails, a centralized reading center can unify the methods. Because the goals of research examinations are different from those of clinical examinations, screening and diagnostic clinical examinations may require fewer velocity measurements.</p

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Intracranial collateralization determines hemodynamic forces for carotid plaque disruption

IntroductionPercent diameter reduction provides an imperfect assessment of the risk for stroke from carotid atheroembolism. Stroke associated with atherosclerotic carotid stenosis commonly results from plaque disruption brought about by hemodynamic shear stress and Bernoulli forces. The aim of the present study was to predict the effect of incomplete intracranial collateralization through the circle of Willis (COW) on disruptive hemodynamic forces acting on carotid plaques.MethodsA simple circuit model of the major pathways and collaterals that form and supply the COW was developed. We modeled the intra- and extracranial arterial circuits from standard anatomic references, and the pressure-flow relationships within these conduits from standard fluid mechanics. The pressure drop caused by (laminar and turbulent) flow along the internal carotid artery path was then computed. Carotid circulation to the brain was classified as being with or without collateral connections through the COW, and the extracranial carotid circuit as being with or without severe stenosis. The pressure drop was computed for each scenario. Finally, a linear circuit model was used to compute brain blood flow in the presence/absence of a disconnected COW.ResultsPressure drop across a carotid artery stenosis increased as the flow rate within the carotid conduit increased. Poststenotic turbulence from a sudden expansion distal to the stenosis resulted in an additional pressure drop. Despite the stenosis, mean brain blood flow was sustained at 4.15 mL/s bilaterally. In the presence of an intact (collateralized) COW, this was achieved by enhanced flow in the contralateral (normal) carotid artery. However, in a disconnected COW, this was achieved by sustained systolic and enhanced diastolic flow through the stenosed artery. For a similar degree of stenosis, flow and velocity across the plaque was much higher when the COW was disconnected compared with an intact COW. Furthermore, the pressure drop across a similar stenosis was significantly higher with a disconnected COW compared with an intact COW.ConclusionsIncomplete intracranial collateralization through the COW results in increased flow rates and velocities, and therefore large pressure drops across a carotid artery stenosis. This exerts large disruptive shear stress on the plaque compared with patients with an intact COW. Percent diameter reduction provides an inaccurate assessment of risk for atheroembolic stroke. An assessment of carotid flow rates, flow velocities, and the intracranial collateral circulation may add independent information to refine the estimation of stroke risk in patients with asymptomatic carotid atherosclerosis.Clinical RelevancePercent carotid narrowing is not an accurate method to assess risk of stroke in patients with carotid stenosis. Stroke from carotid stenosis results from plaque disruption and atheroembolization. We developed a computer model of blood flow through the carotid and intracranial system. We found that high carotid flow rates and velocities, and not tight stenosis alone, resulted in high disruptive shear stress and Bernoulli forces on the plaque. The highest flow rates occurred in individuals without intracranial collateralization. Therefore, carotid flow rates, velocities, and the integrity of the circle of Willis determine risk for carotid plaque disruption, independent of degree of stenosis

Ultrasound and Carotid Bifurcation Atherosclerosis

XVII, 649p. 278 illus., 195 illus. in color.onlin

Noninvasive measurement of local arterial pulse wave velocity in humans by ultrasound

An improved method for noninvasive measurement of the local velocity of arterial pulse wave propagation by an echo-tracking-based ultrasound system is described. A data acquisition image interface was programmed in the ultrasound machine simultaneously to record M-mode ultrasound signals at two locations of a given distance apart along an artery. The selections of measurement sites, separation, and time resolution were performed on the control interface. The temporal sampling frequency could be as high as 10 kHz. The displacements of the blood vessel wall along the time axis were calculated from the M-mode signals by cross-correlation of the radio-frequency data and the distension waveforms were obtained. The temporal separation of the feet of the distension curves from the two measurement locations was derived to give the travel time of the pulse wave. Measurements were made in vivo on human carotid arteries. The pulse wave velocities measured from four volunteers were from 4.1 to 7.2 m/s with coefficients of variation from 5.9 to 29.5%. Some of the factors contributing to the variation in measured values of the velocity are discussed. The method is simple to implement and should be suitable for clinical research into local pulse wave velocity