Computational Fluid Dynamic Simulations for Determination of Ventricular Workload in Aortic Arch Obstructions

Objective The cardiac workload associated with various types of aortic obstruction was determined using computational fluid dynamic simulations. Methods Computed tomography image data were collected from 4 patients with 4 distinct types of aortic arch obstructions and 4 controls. The categorization of arch hypoplasia corresponded to the “A, B, C” nomenclature of arch interruption; a type “D” was added to represent diffuse arch hypoplasia. Measurements of the vessel diameter were compared against the normal measurements to determine the degree of narrowing. Three-dimensional models were created for each patient, and additional models were created for type A and B hypoplasia to represent 25%, 50%, and 75% diameter narrowing. The boundary conditions for the computational simulations were chosen to achieve realistic flow and pressures in the control cases. The simulations were then repeated after changing the boundary conditions to represent a range of cardiac and vascular adaptations. The resulting cardiac workload was compared with the control cases. Results Of the 4 patients investigated, 1 had aortic coarctation and 3 had aortic hypoplasia. The cardiac workload of the patients with 25% narrowing type A and B hypoplasia was not appreciably different from that of the control. When comparing the different arch obstructions, 75% type A, 50% type B, and 50% type D hypoplasia required a greater workload increase than 75% coarctation. Conclusions The present study has determined the hemodynamic significance of aortic arch obstruction using computational simulations to calculate the cardiac workload. These results suggest that all types of hypoplasia pose more of a workload challenge than coarctation with an equivalent degree of narrowing

Antidepressants and Breast and Ovarian Cancer Risk: A Review of the Literature and Researchers' Financial Associations with Industry

BACKGROUND: Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions. METHODS AND FINDINGS: We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03-1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher's Exact test P = 0.0012). CONCLUSIONS: Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the informed consent process

Computational simulations of hemodynamic changes within thoracic, coronary, and cerebral arteries following early wall remodeling in response to distal aortic coarctation

Mounting evidence suggests that the pulsatile character of blood pressure and flow within large arteries plays a particularly important role as a mechano-biological stimulus for wall growth and remodeling. Nevertheless, understanding better the highly coupled interactions between evolving wall geometry, structure, and properties and the hemodynamics will require significantly more experimental data. Computational fluid–solid-growth models promise to aid in the design and interpretation of such experiments and to identify candidate mechanobiological mechanisms for the observed arterial adaptations. Motivated by recent aortic coarctation models in animals, we used a computational fluid–solid interaction model to study possible local and systemic effects on the hemodynamics within the thoracic aorta and coronary, carotid, and cerebral arteries due to a distal aortic coarctation and subsequent spatial variations in wall adaptation. In particular, we studied an initial stage of acute cardiac compensation (i.e., maintenance of cardiac output) followed by early arterial wall remodeling (i.e., spatially varying wall thickening and stiffening). Results suggested, for example, that while coarctation increased both the mean and pulse pressure in the proximal vessels, the locations nearest to the coarctation experienced the greatest changes in pulse pressure. In addition, after introducing a spatially varying wall adaptation, pressure, left ventricular work, and wave speed all increased. Finally, vessel wall strain similarly experienced spatial variations consistent with the degree of vascular wall adaptation

Finite element study of a lumbar intervertebral disc nucleus replacement device

Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3-L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3-L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics compared with the normal intact nucleus