Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies.

BACKGROUND: Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring. METHODS AND RESULTS: We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7±1.6% versus 8.6±1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally. CONCLUSIONS: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.

Disentangling the Hettangian carbon isotope record: Implications for the aftermath of the end-Triassic mass extinction

This study provides an organic carbon stable isotope (delta(13)C(org)) record calibrated with detailed ammonite biostratigraphy, following the end-Triassic biological crisis. Precise correlation between this crucial fossil group and the delta(13)C(org) record is key to understanding feedbacks between biological and environmental events following mass extinction. The latest Triassic and Hettangian delta(13)C(org) record shows several negative and positive excursions. The end-Triassic negative shift coinciding with the mass extinction interval is followed by a positive excursion in the earliest Hettangian Psiloceras spelae beds, which marks the onset of recovery in the marine ecosystem. This positive trend is interrupted by a second negative delta(13)C(org) excursion in the P. pacificum beds related to a minor ammonite extinction event. This pattern of the delta(13)C(org) curve culminates in the uppermost Hettangian Angulata Zone major positive excursion. This indicates that both the ecosystem and the carbon cycle remained in a state of perturbation for at least 2 Ma, although the recovery of some pelagic taxa already began at the base of Jurassic. The early and late Hettangian positive delta(13)C(org) excursions have been confused in several recent papers. Here, we show that during the Hettangian there are indeed two distinct positive delta(13)C(org) excursions. Phases of anoxia and further pulses of Central Atlantic Magmatic Province volcanism during the Hettangian might have inhibited the full recovery for that interval of time. The main Liasicus-Angulata organic positive CIE (carbon isotope excursion) during the Late Hettangian might be related to gradual decreasing of pCO(2) due to protracted high organic burial, and coincides with a second phase of recovery, as indicated by a pulse of ammonoid diversification.

Bond Development in Concrete Overlays, August 1995

Data collection to determine the rate of bond strength development between concrete overlays and existing pavements and the evaluation of nondestructive testing methods for determining concrete strength were the objectives of this study. Maturity meters and pulse velocity meters were employed to determine the rate of flexural strength gain and determine the time for opening of newly constructed pavements to traffic. Maturity measurements appear to provide a less destructive method of testing. Pulse velocity measurements do require care in the preparation of the test wells and operator care in testing. Both devices functioned well under adverse weather and construction conditions and can reduce construction traffic delay decisions. Deflection testing and strain gaging indicate differences in the reaction of the overlay and existing pavement under grouting versus nongrouted sections. Grouting did enhance the rate of bond development with Type I11 cement out performing the Type I1 grout section. Type I11 and Type I1 cement grouts enhanced resistance to cracking in uniformly supported pavements where joints are prepared prior to overlays achieving target flexural strengths. Torsional and direct shear testing provide additional ways of measuring bond development at different cure times. Detailed data analysis will be utilized by TRANSTEC, Inc. to develop a bonded overlay construction guidelines report.

Renal arteries: navigator-gated balanced fast field-echo projection MR angiography with aortic spin labeling: initial experience.

A cardiac-triggered free-breathing three-dimensional balanced fast field-echo projection magnetic resonance (MR) angiographic sequence with a two-dimensional pencil-beam aortic labeling pulse was developed for the renal arteries. For data acquisition during free breathing in eight healthy adults and seven consecutive patients with renal artery disease, real-time navigator technology was implemented. This technique allows high-spatial-resolution and high-contrast renal MR angiography and visualization of renal artery stenosis without exogenous contrast agent or breath hold. Initial promising results warrant larger clinical studies.

A fast 3D approach for coronary MRA.

Two-dimensional (2D)-breath-hold coronary magnetic resonance angiography (MRA) has been shown to be a fast and reliable method to depict the proximal coronary arteries. Recent developments, however, allow for free-breathing navigator gated and navigator corrected three-dimensional (3D) coronary MRA. These 3D approaches have potential for improved signal-to-noise ratio (SNR) and allow for the acquisition of adjacent thin slices without the misregistration problems known from 2D approaches. Still, a major impediment of a 3D acquisition is the increased scan time. The purpose of this study was the implementation of a free-breathing navigator gated and corrected ultra-fast 3D coronary MRA technique, which allows for scan times of less than 5 minutes. Twelve healthy adult subjects were examined in the supine position using a navigator gated and corrected ECG triggered ultra-fast 3D interleaved gradient echo planar imaging sequence (TFE-EPI). A 3D slab, consisting of 20 slices with a reconstructed slice thickness of 1.5 mm, was acquired with free-breathing. The diastolic TFE-EPI acquisition block was preceded by a T2prep pre-pulse, a diaphragmatic navigator pulse, and a fat suppression pre-pulse. With a TR of 19 ms and an effective TE of 5.4 ms, the duration of the data acquisition window duration was 38 ms. The in-plane spatial resolution was 1.0-1.3 mm*1.5-1.9 mm. In all cases, the entire left main (LM) and extensive portions of the left anterior descending (LAD) and right coronary artery (RCA) could be visualized with an average scan time for the entire 3D-volume data set of 2:57 +/- 0:51 minutes. Average contiguous vessel length visualized was 53 +/- 11 mm (range: 42 to 75 mm) for the LAD and 84 +/- 14 mm (range: 62 to 112 mm) for the RCA. Contrast-to-noise between coronary blood and myocardium was 5.0 +/- 2.3 for the LM/LAD and 8.0 +/- 2.9 for the RCA, resulting in an excellent suppression of myocardium. We present a new approach for free-breathing 3D coronary MRA, which allows for scan times superior to corresponding 2D coronary MRA approaches, and which takes advantage of the enhanced SNR of 3D acquisitions and the post-processing benefits of thin adjacent slices. The robust image quality and the short average scanning time suggest that this approach may be useful for screening the major coronary arteries or identification of anomalous coronary arteries. J. Magn. Reson. Imaging 1999;10:821-825.

Film-free laser forward printing of transparent and weakly absorbing liquids

A laser-based technique for printing transparent and weakly absorbing liquids is developed. Its principle of operation relies in the tight focusing of short laser pulses inside the liquid and close to its free surface, in such a way that the laser radiation is absorbed in a tiny volume around the beam waist, with practically no absorption in any other location along the beam path. If the absorbed energy overcomes the optical breakdown threshold, a cavitation bubble is generated, and its expansion results in the propulsion of a small fraction of liquid which can be collected on a substrate, leading to the printing of a microdroplet for each laser pulse. The technique does not require the preparation of the liquid in thin film form, and its forward mode of operation imposes no restriction concerning the optical properties of the substrate. These characteristics make it well suited for printing a wide variety of materials of interest in diverse applications. We demonstrate that the film-free laser forward printing technique is capable of printing microdroplets with good resolution, reproducibility and control, and analyze the influence of the main process parameter, laser pulse energy. The mechanisms of liquid printing are also investigated: time-resolved imaging provides a clear picture of the dynamics of liquid transfer which allows understanding the main features observed in the printed droplets.

Influence of the dipolar interactions in the magnetization reversal asymmetry of hard-soft magnetic ribbons

Partial crystallization of the metallic glass Co66Si16B12Fe4Mo2 was performed by annealing at temperatures between 500 and 540°C for 10-20 min, resulting in crystallite volume fractions of (0.7-5)×10¿3 and sizes of 50-100 nm. This two-phase alloy presents a remarkable feature: a hysteresis loop shift that can be tailored by simply premagnetizing the sample in the adequate magnetic field. Shifts as large as five times the coercive field have been obtained which make them interesting for application as magnetic cores in dc pulse transformers. The asymetrical magnetic reversal is explained in terms of the magnetic dipolar field interaction and the observed hysteresis loops have been satisfactorily simulated by a modification of Stoner-Wohlfarth¿s model of coherent rotations.

Laser-induced forward transfer of liquids: Study of the droplet ejection process

Laser-induced forward transfer (LIFT) is a laser direct-write technique that offers the possibility of printing patterns with a high spatial resolution from a wide range of materials in a solid or liquid state, such as conductors, dielectrics, and biomolecules in solution. This versatility has made LIFT a very promising alternative to lithography-based processes for the rapid prototyping of biomolecule microarrays. Here, we study the transfer process through the LIFT of droplets of a solution suitable for microarray preparation. The laser pulse energy and beam size were systematically varied, and the effect on the transferred droplets was evaluated. Controlled transfers in which the deposited droplets displayed optimal features could be obtained by varying these parameters. In addition, the transferred droplet volume displayed a linear dependence on the laser pulse energy. This dependence allowed determining a threshold energy density value, independent of the laser focusing conditions, which acted as necessary conditions for the transfer to occur. The corresponding sufficient condition was given by a different total energy threshold for each laser beam dimension. The threshold energy density was found to be the dimensional parameter that determined the amount of the transferred liquid per laser pulse, and there was no substantial loss of material due to liquid vaporization during the transfer.

Time-resolved imaging of the laser forward transfer of liquids

Time-resolved imaging is carried out to study the dynamics of the laser-induced forward transfer of an aqueous solution at different laser fluences. The transfer mechanisms are elucidated, and directly correlated with the material deposited at the analyzed irradiation conditions. It is found that there exists a fluence range in which regular and well-defined droplets are deposited. In this case, laser pulse energy absorption results in the formation of a plasma, which expansion originates a cavitation bubble in the liquid. After the further expansion and collapse of the bubble, a long and uniform jet is developed, which advances at a constant velocity until it reaches the receptor substrate. On the other hand, for lower fluences no material is deposited. In this case, although a jet can be also generated, it recoils before reaching the substrate. For higher fluences, splashing is observed on the receptor substrate due to the bursting of the cavitation bubble. Finally, a discussion of the possible mechanisms which lead to such singular dynamics is also provided.

Electrical colonic stimulation reduces mean transit time in a porcine model.

Abstract Electrical stimulation is a new way to treat digestive disorders such as constipation. Colonic propulsive activity can be triggered by battery operated devices. This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic examination of the caecum was routinely performed after animal sacrifice. A reduction of mean transit time was observed after electrical stimulation (19 +/- 13 h; mean +/- SD) when compared to reference (34 +/- 7 h; P = 0.045) and mean transit time after sham stimulation (36 +/- 9 h; P = 0.035). Histological examination revealed minimal chronic inflammation around the electrodes. Colonic transit time measured in a chronic porcine model is reduced by direct sequential electrical stimulation. Minimal tissue lesion is elicited by stimulation or implanted material. Electrical colonic stimulation could be a promising approach to treat specific disorders of the large bowel.

Synchronization, diversity, and topology of networks of integrate and fire oscillators

We study synchronization dynamics of a population of pulse-coupled oscillators. In particular, we focus our attention on the interplay between topological disorder and synchronization features of networks. First, we analyze synchronization time T in random networks, and find a scaling law which relates T to network connectivity. Then, we compare synchronization time for several other topological configurations, characterized by a different degree of randomness. The analysis shows that regular lattices perform better than a disordered network. This fact can be understood by considering the variability in the number of links between two adjacent neighbors. This phenomenon is equivalent to having a nonrandom topology with a distribution of interactions and it can be removed by an adequate local normalization of the couplings.

Insulin modulation of luteinizing hormone secretion in normal female volunteers and lean polycystic ovary syndrome patients.

BACKGROUND/AIMS: Endocrine features of polycystic ovary syndrome (PCOS) include altered ovarian steroidogenesis, hyperinsulinemia and abnormal luteinizing hormone (LH) secretion. This study was undertaken to further evaluate the role of insulin to modulate LH secretion in lean PCOS patients with normal insulin sensitivity and normal volunteers. METHODS: The study was performed in five nonobese patients diagnosed with PCOS on the basis of amenorrhea and a polycystic morphology at ovarian ultrasound, and 5 normal controls in early to mid-follicular phase and matched for weight and age. All subjects were phenotyped, and then admitted for 12 h of frequent (q 10') blood sampling on two separate occasions, once for a baseline study and the other time for a hyperinsulinemic and euglycemic clamp study. LH was measured in samples obtained throughout each admission in order to perform LH pulse analysis. RESULTS: Baseline LH secretion in PCOS subjects was significantly different from controls: they had higher LH levels, higher LH/FSH ratios as well as a faster LH pulse frequency than normal women. Insulin administration did not affect the pattern of LH secretion of PCOS patients, whereas it significantly increased the LH pulse frequency while decreasing the LH interpulse intervals in the controls. CONCLUSIONS: These data confirm that an abnormal pattern of LH secretion characteristic of PCOS can be observed in lean patients, and appears independent of peripheral insulin levels. Furthermore, our results in lean controls provide the first direct evidence that peripheral insulin can modulate the activity of hypothalamic gonadotropin-releasing hormone (GnRH) neurons in the human.

The contributions of sensory dominance and attentional bias to cross-modal enhancement of visual cortex excitability.

Approaching or looming sounds (L-sounds) have been shown to selectively increase visual cortex excitability [Romei, V., Murray, M. M., Cappe, C., & Thut, G. Preperceptual and stimulus-selective enhancement of low-level human visual cortex excitability by sounds. Current Biology, 19, 1799-1805, 2009]. These cross-modal effects start at an early, preperceptual stage of sound processing and persist with increasing sound duration. Here, we identified individual factors contributing to cross-modal effects on visual cortex excitability and studied the persistence of effects after sound offset. To this end, we probed the impact of different L-sound velocities on phosphene perception postsound as a function of individual auditory versus visual preference/dominance using single-pulse TMS over the occipital pole. We found that the boosting of phosphene perception by L-sounds continued for several tens of milliseconds after the end of the L-sound and was temporally sensitive to different L-sound profiles (velocities). In addition, we found that this depended on an individual's preferred sensory modality (auditory vs. visual) as determined through a divided attention task (attentional preference), but not on their simple threshold detection level per sensory modality. Whereas individuals with "visual preference" showed enhanced phosphene perception irrespective of L-sound velocity, those with "auditory preference" showed differential peaks in phosphene perception whose delays after sound-offset followed the different L-sound velocity profiles. These novel findings suggest that looming signals modulate visual cortex excitability beyond sound duration possibly to support prompt identification and reaction to potentially dangerous approaching objects. The observed interindividual differences favor the idea that unlike early effects this late L-sound impact on visual cortex excitability is influenced by cross-modal attentional mechanisms rather than low-level sensory processes.

Procedure for human saphenous veins ex vivo perfusion and external reinforcement.

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.

Glucose release from GLUT2-null hepatocytes: characterization of a major and a minor pathway.

We previously reported that glucose can be released from GLUT2-null hepatocytes through a membrane traffic-based pathway issued from the endoplasmic reticulum. Here, we further characterized this glucose release mechanism using biosynthetic labeling protocols. In continuous pulse-labeling experiments, we determined that glucose secretion proceeded linearly and with the same kinetics in control and GLUT2-null hepatocytes. In GLUT2-deficient hepatocytes, however, a fraction of newly synthesized glucose accumulated intracellularly. The linear accumulation of glucose in the medium was inhibited in mutant, but not in control, hepatocytes by progesterone and low temperature, as previously reported, but, importantly, also by microtubule disruption. The intracellular pool of glucose was shown to be present in the cytosol, and, in pulse-chase experiments, it was shown to be released at a relatively slow rate. Release was not inhibited by S-4048 (an inhibitor of glucose-6-phosphate translocase), cytochalasin B, or progesterone. It was inhibited by phloretin, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, and low temperature. We conclude that the major release pathway segregates glucose away from the cytosol by use of a membrane traffic-based, microtubule-dependent mechanism and that the release of the cytosolic pool of newly synthesized glucose, through an as yet unidentified plasma membrane transport system, cannot account for the bulk of glucose release.