Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.This paper has been partially funded by CompBioMed project, under H2020-EU.1.4.1.3 European Union’s Horizon 2020 research and innovation programme, grant agreement n◦ 675451. FS is supported by a grant from Severo Ochoa (n◦ SEV-2015-0493-16-4), Spain. CB is supported by a grant from the Fundació LaMarató de TV3 (n◦ 20154031), Spain. TI and PI are supported by the Institute of Engineering in Medicine, USA, and the Lillehei Heart Institute, USA.Peer ReviewedPostprint (published version

InSAR Scientific Computing Environment

This computing environment is the next generation of geodetic image processing technology for repeat-pass Interferometric Synthetic Aperture (InSAR) sensors, identified by the community as a needed capability to provide flexibility and extensibility in reducing measurements from radar satellites and aircraft to new geophysical products. This software allows users of interferometric radar data the flexibility to process from Level 0 to Level 4 products using a variety of algorithms and for a range of available sensors. There are many radar satellites in orbit today delivering to the science community data of unprecedented quantity and quality, making possible large-scale studies in climate research, natural hazards, and the Earth's ecosystem. The proposed DESDynI mission, now under consideration by NASA for launch later in this decade, would provide time series and multiimage measurements that permit 4D models of Earth surface processes so that, for example, climate-induced changes over time would become apparent and quantifiable. This advanced data processing technology, applied to a global data set such as from the proposed DESDynI mission, enables a new class of analyses at time and spatial scales unavailable using current approaches. This software implements an accurate, extensible, and modular processing system designed to realize the full potential of InSAR data from future missions such as the proposed DESDynI, existing radar satellite data, as well as data from the NASA UAVSAR (Uninhabited Aerial Vehicle Synthetic Aperture Radar), and other airborne platforms. The processing approach has been re-thought in order to enable multi-scene analysis by adding new algorithms and data interfaces, to permit user-reconfigurable operation and extensibility, and to capitalize on codes already developed by NASA and the science community. The framework incorporates modern programming methods based on recent research, including object-oriented scripts controlling legacy and new codes, abstraction and generalization of the data model for efficient manipulation of objects among modules, and well-designed module interfaces suitable for command- line execution or GUI-programming. The framework is designed to allow users contributions to promote maximum utility and sophistication of the code, creating an open-source community that could extend the framework into the indefinite future

Fatigue and damage as a result of exercise in normal and diseased skeletal muscle

This thesis examines the nature of fatigue and damage as it affects healthy and dystrophic skeletal muscle. Initial fatigue studies were carried out using isolated mouse muscles. After 3 min of repeated maximal stimulation, extensor digitorum longus muscle force was reduced to 26% of the fresh value but this could be reversed by the addition of caffeine to the incubation medium, suggesting that acute fatigue is primarily due to failure of the processes of activation. In the human tibialis anterior (TA) muscle it was found that fatigue resulting from stimulated isometric contractions were affected by muscle length. Exercise at short lengths resulted in less force loss at the resting length, whereas exercise at long muscle lengths caused a greater force loss than normal at the resting length. There was a preferential force loss at sub-maximal stimulation frequencies, and this was exacerbated when muscles were exercised in a lengthened positon. Similar changes were observed using isolated mouse soleus muscles. Because of uncertainties about the adequate diffusion of metabolites in isolated muscles the properties of dystrophin-deficient (mdx) mouse muscles were investigated using an in vivo preparation of the TA. The mdx TA was, on average, 30% stronger than that of control mice but had a reduced force/cross-sectional area and a smaller low/high frequency force ratio due to a faster activation time, mdx muscle also displayed a greater fatigue resistance when exercised at a low frequency, but this was not the case with stimulation at maximal frequency. In order to test whether the altered contractile properties of mdx muscle were due to the presence of degenerating and regenerating fibres, the contractile characteristics of normal muscle were investigated during damage and recovery. Damage was induced by stimulated lengthening 1 contractions of the foot dorsiflexor muscles of mice. Maximum force, force-frequency characteristics, and morphology were measured for up to 20 days after exercise. Although the properties of normal/damaged and mdx muscles displayed a number of superficial similarities, it is unlikely that the altered contractile characteristics of mdx muscles are due to the presence of damaged fibres. The possibility that dystrophin-deficient muscles are more susceptible to exercise induced muscle damage was examined by comparing the responses of mdx and norm.al muscles to an episode of eccentric work. The findings were unequivocal, normal and mdx TA muscles displayed similar degrees of force loss 3 days after exercise (55% and 52% respectively) and comparable rates of force recovery after 12 days (76% and 80% of control in normal and mdx muscles respectively). The protective effect afforded by a bout of eccentric exercise against subsequent muscle injury from a similar exercise was characterised. Re-exercising a muscle after 10 days recovery had little effect on the immediate consequences of exercise, but reduced the degree of delayed onset force loss and fibre necrosis. Animals re-exercised after 12 weeks recovery displayed no apparent protection against delayed onset muscle damage when the exercise was repeated. These findings me in general agreement with work carried out in humans, but the time course of recovery post exercise is at least three times faster in the mouse, which has made a study of the long-term effects of eccentric exercise more practical. Six weeks after exercise, increases in muscle mass and force were evident, with a proportion of fibres displaying internal nuclei and signs of fibre splitting. Surprisingly, greater forces and fibre hypertrophy also occurred after 12 weeks recovery from an episode of eccentric work

Taking the Edge Off: The Role of Stressful Events and Perceived Stress on Alcohol Use and Problems Among Older Adults

Alcohol misuse by older adults is a significant public health concern and is projected to worsen with the aging of the baby boom generation. To help understand the nature of older adult alcoholism, it is crucial to investigate factors such as stress that may influence consumption and problem use among older adults. Findings are mixed on the role of stress and coping in alcohol use, and studies comparing the role of stress and coping in alcohol use on different age groups are rare. Therefore, this study had the following aims: 1) To test a stress and coping model of current alcohol use, at-risk drinking, and alcohol-related problems in a nationally representative sample of older adults; 2) To investigate cohort differences in the Stress and Coping model between young adult: 20-39), early middle age: 40-59), and older adult: 60+) life stages. This investigator conducted secondary analysis of the National Epidemiologic Survey of Alcohol and Related Conditions: NESARC). An overall model of stress and coping was tested using structural equation modeling: SEM) with a subsample of older adult, middle-aged, and young adult current drinkers. Multiple group models tested group differences in the overall model, and interaction tests were conducted to test for a stress buffering effect of social support. Older adults endorsed lower levels of stressful life events, cognitive appraisal of stress and social support than younger age groups; alcohol consumption, at-risk drinking and rate of alcohol problems were also lower. In all age groups, higher levels of stressful events were associated with cognitive appraisal of stress, but in older adults, cognitive appraisal was associated with decreases in alcohol use. Among younger age groups, cognitive appraisal was associated with problem use, but not at-risk drinking or increased consumption. Interaction models were nonsignificant, suggesting that social support does not buffer the effect of stressful events on cognitive appraisal. The overall findings highlight limits of a global stress and coping model of alcohol use. Implications include the need to consider contextual and developmental factors in stress-related drinking including unique stresses in late life, and changing relationships between stress and drinking in older adulthood

Parental Assets and Children\u27s Educational Outcomes

Several countries, including Canada, Singapore and the United Kingdom, have enacted asset-based policies for children in recent years. The premise underlying these policies is that increases in assets lead to improvement in various child outcomes over time. But little existing research examines this premise from a dynamic perspective. Using data from the NLSY79 mother and child datasets, two parallel process latent growth curve models are estimated to examine the effects of parental asset accumulation on changes in children’s math and reading achievement over six years during middle childhood. Results indicate that the initial level of assets is positively associated with math scores but not reading scores, while higher rates of asset accumulation are associated with slower rates of decline in reading scores but has no effect on changes in math scores. Overall, the results suggest that the relationship between assets and various child outcomes may not be straightforward. Different dimensions of the asset experience may lead to different outcomes, and the same dimension may also have different effects. Implications for future research and for asset-based policies are discussed

Changes In Parental Assets And Children\u27s Educational Outcomes

Several countries, including Canada, Singapore and the United Kingdom, have enacted asset-based policies for children in recent years. The premise underlying these policies is that increases in assets lead to improvement in various child outcomes over time. But little existing research examines this premise from a dynamic perspective. Using data from the NLSY79 mother and child datasets, two parallel process latent growth curve models are estimated to examine the effects of parental asset accumulation on changes in children\u27s achievements over six years during middle childhood. Results indicate that the initial level of assets is positively associated with math scores, but not reading scores, while faster asset accumulation is associated with changes in reading scores, but not in math scores. Overall, the results suggest that the relationship between assets and various child outcomes may not be straight-forward. Different dimensions of the asset experience may lead to different outcomes, and the same dimension may also have different effects. Implications for future research and for asset-based policies are discussed

A Review of Existing Treatments for Substance Abuse Among the Elderly and Recommendations for Future Directions

Background: With population aging, there is widespread recognition that the healthcare system must be prepared to serve the unique needs of substance using older adults (OA) in the decades ahead. As such, there is an increasingly urgent need to identify efficient and effective substance abuse treatments (SAT) for OA. Despite this need, there remains a surprising dearth of research on treatment for OA. Aims of review: This review describes and evaluates studies on SAT applied to and specifically designed for OA over the last 30 years with an emphasis on methodologies used and the knowledge gained. Methods: Using three research databases, 25 studies published in the last 30 years which investigated the impact of SAT on OA and met specific selection criteria were reviewed. Results: A majority of the studies were methodologically limited in that they were pre-to-post or post-test only studies. Of the randomized controlled trials, many were limited by sample sizes of 15 individuals or less per group, making main effects difficult to detect. Thus, with caution, the literature suggests that among treatment seeking OA, treatment, whether age-specific or mixed-age, generally works yielding rates of abstinence comparable to general populations and younger cohorts. It also appears that with greater treatment exposure (higher dosage), regardless of level of care, OA do better. Finally, based on only two studies, age-specific treatment appears to potentiate treatment effects for OA. Like younger adults, OA appear to have a heterogeneous response to treatments, and preliminary evidence suggests a possibility of treatment matching for OA. Conclusions: Expansion of research on SAT for OA is urgently needed for maximum effectiveness and efficiency of the healthcare system serving these individuals. Future research needs to include laboratory and community based randomized controlled trials with high internal validity of previously vetted evidenced-based practices, including Motivational Interviewing, cognitive behavioral therapy, and medications such as naltrexone, to determine the best fit for OA

Deferiprone versus Deferoxamine in Sickle Cell Disease: Results from a 5-year long-term Italian multi-center randomized clinical trial.

Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although the basal serum ferritin levels were higher in transfused compared with non-transfused group (p=0.031), the changes over time in serum ferritin levels were not statistically significantly different between transfused and non-transfused cohort of patients (p=0.389). Kaplan-Meier curve, during 5-years of study, suggests that Deferiprone does not alter survival in comparison with Deferoxamine (p=0.38). In conclusion, long-term iron chelation therapy with Deferiprone was associated with efficacy and safety similar to that of Deferoxamine. Therefore, in patients with Sickle-Cell-Disease, Deferiprone may represent an effective long-term treatment option

Design and Development of a Deep Acoustic Lining for the 40-by 80-Foot Wind Tunnel Test Section

The work described in this report has made effective use of design teams to build a state-of-the-art anechoic wind-tunnel facility. Many potential design solutions were evaluated using engineering analysis, and computational tools. Design alternatives were then evaluated using specially developed testing techniques, Large-scale coupon testing was then performed to develop confidence that the preferred design would meet the acoustic, aerodynamic, and structural objectives of the project. Finally, designs were frozen and the final product was installed in the wind tunnel. The result of this technically ambitious project has been the creation of a unique acoustic wind tunnel. Its large test section (39 ft x 79 ft x SO ft), potentially near-anechoic environment, and medium subsonic speed capability (M = 0.45) will support a full range of aeroacoustic testing-from rotorcraft and other vertical takeoff and landing aircraft to the take-off/landing configurations of both subsonic and supersonic transports