Impact of pulmonary vascular stiffness and vasodilator treatment in pediatric pulmonary hypertension: 21 patient-specific fluid-structure interaction studies

Recent clinical studies of pulmonary arterial hypertension (PAH) have found correlations between increased pulmonary vascular stiffness (PVS) and poorer disease outcomes. However, mechanistic questions remain about the relationships amongst PVS, RV power, and vascular hemodynamics in the setting of progressive PAH that are difficult or impossible to answer using direct measurements. Clinically validated patient-specific computational modeling may allow exploration of these issues through perturbation-based predictive testing. Here we use a simple patient-specific model to answer four questions: how do hemodynamics change as PAH worsens? How does increasing PVS impact hemodynamics and RV power? For a patient with moderate PAH, what are the consequences if the pressures increase modestly yet sufficiently to engage collagen in those vessels? What impact does pressure-reducing vasodilator treatment have on hemodynamics? Twenty-one sets of model-predicted impedance and mean PA pressure (mPAP) show good agreement with clinical measurements, thereby validating the model. Worsening was modeled using data from three PAH outcomes groups; these show not only the expected increase in mPAP, but also an increase in pressure pulsatility. Interestingly, chronically increasing mPAP decreased WSS, suggesting that increased PA cross-sectional area affected WSS greater than increased PVS. For a patient with moderately high PVR (12.7 WU) with elastin-based upstream vascular remodeling, moving from elastin-dominant vessel behavior to collagen-dominant behavior caused substantial increases in mPAP, pressure and WSS pulsatility. For the same patient, reducing PVR through a simulated vasodilator to a value equivalent to mild PAH did not decrease pressure pulsatility and dramatically increased WSS pulsatility. Overall, these results suggest a close association between PVS and hemodynamics and that hemodynamics may play an important role in progressing PAH. These support the hypothesis that treatments should target decreasing or reversing upstream vascular remodeling in addition to decreasing mean pressures.     

Histopathologic spectrum of vaginal adenosis and related changes in stilbestrol-exposed females

A total of 98 colposcopically directed biopsies were obtained from the vagina, cervix, and cervicovaginal ridge (hood) of 80 young women believed to have had intrauterine exposure to stilbestrol (DES). Specific investigation of the patient's medical records corroborated the history of maternal stilbestrol administration in 36 patients (45%), while in the remainder the drug history was regarded as presumptive since medical records were unavailable for review. The findings did not differ significantly in those biopsies taken from patients with confirmed or presumptive drug histories. Histologic evidence of vaginal adenosis was detected in vaginal biopsies from 43 patients. In 30 cases (70%) benign Müllerian-type glandular epithelium was in the superficial vaginal wall, residing on the mucosal surface and/or in the lamina propria. The glandular epithelium predominantly was of endocervical type, but in six instances it resembled endometrial or fallopian tubal epithelium. The glands were accompanied by varying degrees of squamous metaplasia in 22 cases. When extensive the metaplasia produced transformation zones similar to those seen in the normal cervix. Vaginal biopsies of adenosis from the other 13 patients (30%) revealed squamous metaplasia without demonstrable glands due to complete transformation of all antecedent glandular epithelium by squamous metaplasia. Our studies indicate that squamous metaplasia is a component of major importance in the natural history of adenosis and that the concept of adenosis should be broadened to include those examples comprised exclusively of metaplastic epithelium. In such examples metaplasia is identified by the immaturity and poor glycogenation of the squamous cells and their accompanying squamous pegs which often contain residual gland openings or squamous "eddies." Similar findings were present in biopsies of seven cervicovaginal ridges and in cervical biopsies from 37 patients, except for the absence of endometrial or tubal type glands in the latter site. Although no adenocarcinomas were detected, six patients had squamous dysplasia of the vagina and/or cervix. In no case were premalignant or dysplastic changes of glandular cells found. Our findings support the thesis that stilbestrol-associated adenosis represents anomalous embryologic localization of the original squamocolumnar junction in the vagina rather than in the cervix. It is closely related to so-called cervical "erosions." The development of squamous metaplasia accounts for modifications in the clinical and histologic appearances by producing transformation zones which then may be subject to the same oncogenic stimuli for squamous neoplasia as are their counterparts in the cervix.     

Alterations of normal left ventricular performance by general anesthesia

Serial invasive and noninvasive (systolic time interval) measurements of left ventricular performance were obtained in six healthy volunteers during general anesthesia employing the following sequence: thiopental induction, succinylcholine (prior to endotracheal intubation), and halothane--100 per cent oxygen at 1.25 and 1.75 MAC. Heart rate (HR), mean pulmonary arterial "wedge" pressure (PAW) and mean systemic arterial pressure (MAP) were measured continuously; cardiac index and systolic time intervals (STI's) were measured during each intervention. At both levels of halothane, MAP and stroke work index decreased (both P less than 0.02), while HR and systemic vascular resistance did not change. At 1.25 MAC halothane PAW was unchanged, but at 1.75 MAC PAW increased from 8 +/- 4 (SD) to 11 +/- 5 torr (P less than 0.02). Preload was altered at 1.25 MAC by administration of 600-1,000 ml lactated Ringer's solution; PAW increased from 9 +/- 4 to 17 +/- 3 torr (P less than 0.01). At 1.75 MAC halothane, volume expansion increased PAW in a similar manner, but the resultant ventricular function curve was depressed compared with 1.25 MAC halothane. In additon, at each level of halothane anesthesia, the ventricular function curve was depressed compared with results obtained in awake normal subjects. Afterload was altered at 1.25 MAC halothane by infusion of phenylephrine sufficient to raise MAP by 30 per cent. This intervention resulted in a greater depression of cardiac performance than that observed at 1.75 MAC halothane alone. Although alterations in STI's were directionally similar to changes observed in invasive hemodynamic measurements, STI's were sensitive to acute alternations in loading conditions. It is concluded that the levels of halothane commonly employed for general anesthesia significantly depress left ventricular performance in normal subjects, as evidenced by abnormal responses to alterations in preload and afterload, and that STI's should not be employed for routine measurement of left ventricular performance during anesthesia unless both the afterload and the preload on the myocardium are known.     

Measuring hydraulic properties of geotextiles after installation damage

Since geotextiles have been progressively incorporated into coastal protection structures, the influence of installation damage on them has been the primary concern. During installation/construction, geotextiles are repeatedly subjected to high mechanical stresses which often exceed service stress. It is therefore vital to evaluate the mechanical and hydraulic damage and determine the consequences of these damages to better develop criteria for selection of suitable products. As these damages could reduce the material's mechanical strength and hydraulic efficiency, or in the severest form of damage, puncturing, would end the separation function. The properties investigated in this paper include the permittivity and apparent opening size (AOS) of geotextiles. Generally, the greater the drop energy of armour units applied to geotextiles, the greater the potential for damage. Findings show that the residual permittivity could increase significantly, 45% during installation. The preliminary design of coastal structures will be optimised as engineers and designers can better estimate the amount of damage on geotextiles upon installation.     

A graph coloring constructive hyper-heuristic for examination timetabling problems

In this work we investigate a new graph coloring constructive hyper-heuristic for solving examination timetabling problems. We utilize the hierarchical hybridizations of four low level graph coloring heuristics, these being largest degree, saturation degree, largest colored degree and largest enrollment. These are hybridized to produce four ordered lists. For each list, the difficulty index of scheduling the first exam is calculated by considering its order in all lists to obtain a combined evaluation of its difficulty. The most difficult exam to be scheduled is scheduled first (i.e. the one with the minimum difficulty index). To improve the effectiveness of timeslot selection, a?roulette wheel selection mechanism is included in the algorithm to probabilistically select an appropriate timeslot for the chosen exam. We test our proposed approach on the most widely used un-capacitated Carter benchmarks and also on the recently introduced examination timetable dataset from the 2007 International Timetabling Competition. Compared against other methodologies, our results demonstrate that the graph coloring constructive hyper-heuristic produces good results and outperforms other approaches on some of the benchmark instances.     

Thermal performance comparisons between passive solar and conventional housing in an Irish climate

The thermal performance of a passive solar house in Ireland having high energy conservation standards is compared with that of a similar sized conventional dwelling house. In both cases the performance over a meteorological Test Reference Year is assessed using climatically responsive models developed experimentally which predict their internal temperature without heating.

The results indicate that the conventional house required over three times as much auxiliary heating as the passive solar house. Solar gain accounted for over half the gross heat demand in the solar house compared to 13% in the bungalow. An added advantage of the increased utilization of solar gain was the estimated reduction in the heating season from nine to six months.     

Novel temperature measurement method & thermodynamic investigations of amorphous polymers during high rate deformation

Polymers are frequently used in applications in which they may be exposed to high rate or impact loading, and there is growing industrial importance in understanding their mechanical behavior at different strain rates. An important aspect of this is the temperature rise due to adiabatic conditions in high rate loading. This paper describes research that has been performed to measure the temperature rise that occurs in specimens undergoing rapid deformation. A novel thermocouple design is presented and applied to PMMA and 20 wt% DINP-plasticized PVC, deformed at moderate and high strain rates. The measurements are accompanied by investigations of strain energy.     

The DOE advanced gas reactor fuel development and qualification program

The high outlet temperatures and high thermal-energy conversion efficiency of modular high-temperature gas-cooled reactors (HTGRs) enable an efficient and cost-effective integration of the reactor system with non-electricity-generation applications, such as process heat and/or hydrogen production, for the many petrochemical and other industrial processes that require temperatures between 300°C and 900°C. The U.S. Department of Energy (DOE) has selected the HTGR concept for the Next Generation Nuclear Plant (NGNP) Project as a transformative application of nuclear energy that will demonstrate emissions-free nuclear-assisted electricity, process heat, and hydrogen production, thereby reducing greenhouse-gas emissions and enhancing energy security. The objective of the DOE Advanced Gas Reactor (AGR) Fuel Development and Qualification program is to qualify tristructural isotropic (TRISO)-coated particle fuel for use in HTGRs. An overview of the program and recent progress is presented.     

Fibre diffraction in the analysis of filamentous virus structure

In many plant and bacterial viruses, a filamentous nucleocapsid makes up the entire virus particle. These viruses usually form fibres naturally, but they do not crystallize. Fibre diffraction has therefore been the method of choice for structural studies, aided in recent years by cryo-electron microscopy (EM) and solid state nuclear magnetic resonance (ssNMR). Filamentous viruses, particularly tobacco mosaic virus (TMV), have been important in developing fibre diffraction methods, and fibre diffraction allowed TMV to be among the first virus structures determined. Structures of several viruses related to TMV and several filamentous bacterial viruses have been determined at resolutions of 3?Å or better, and lower resolution structures have been determined by fibre diffraction, sometimes in conjunction with other methods, for many other, unrelated, filamentous viruses.