Metabolomics and cancer preventive behaviors in the BC Generations Project.

Metabolomics can detect metabolic shifts resulting from lifestyle behaviors and may provide insight on the relevance of changes to carcinogenesis. We used non-targeted nuclear magnetic resonance to examine associations between metabolic measures and cancer preventive behaviors in 1319 participants (50% male, mean age 54 years) from the BC Generations Project. Behaviors were dichotomized: BMI < 25 kg/m2, ≥ 5 servings of fruits or vegetables/day, ≤ 2 alcoholic drinks/day for men or 1 drink/day for women and ≥ 30 min of moderate or vigorous physical activity/day. Linear regression was used to estimate coefficients and 95% confidence intervals with a false discovery rate (FDR) of 0.10. Of the 218 metabolic measures, 173, 103, 71 and 6 were associated with BMI, fruits and vegetables, alcohol consumption and physical activity. Notable findings included negative associations between glycoprotein acetyls, an inflammation-related metabolite with lower BMI and greater fruit and vegetable consumption, a positive association between polyunsaturated fatty acids and fruit and vegetable consumption and positive associations between high-density lipoprotein subclasses with lower BMI. These findings provide insight into metabolic alterations in the context of cancer prevention and the diverse biological pathways they are involved in. In particular, behaviors related to BMI, fruit and vegetable and alcohol consumption had a large metabolic impact.

Near Real-Time Implementation of An Adaptive Seismocardiography - ECG Multimodal Framework for Cardiac Gating.

Objective: Accurate gating for data acquisition of computed tomography (CT) is crucial to obtaining high quality images for diagnosing cardiovascular diseases. To illustrate the feasibility of an optimized cardiac gating strategy, we present a near real-time implementation based on fusing seismocardiography (SCG) and ECG. Methods: The implementation was achieved via integrating commercial hardware and software platforms. Testing was performed on five healthy subjects (age: 24-27; m/f: 4/1) and three cardiac patients (age: 41-71; m/f: 2/1), and compared with baseline quiescence derived from echocardiography. Results: The average latency introduced by computerized processing was 5.1 ms, well within a 100 ms tolerance bounded by data accumulation time for quiescence prediction. The average prediction error associated with conventional ECG-only versus SCG-ECG-based method over all subjects were 59.58 ms and 27.24 ms, respectively. Discussion: The results demonstrate that the multimodal framework can achieve improved quiescence prediction accuracy over the ECG-only-based method in near real-time.

An Adaptive Seismocardiography (SCG)-ECG Multimodal Framework for Cardiac Gating Using Artificial Neural Networks.

To more accurately trigger data acquisition and reduce radiation exposure of coronary computed tomography angiography (CCTA), a multimodal framework utilizing both electrocardiography (ECG) and seismocardiography (SCG) for CCTA prospective gating is presented. Relying upon a three-layer artificial neural network that adaptively fuses individual ECG- and SCG-based quiescence predictions on a beat-by-beat basis, this framework yields a personalized quiescence prediction for each cardiac cycle. This framework was tested on seven healthy subjects (age: 22-48; m/f: 4/3) and eleven cardiac patients (age: 31-78; m/f: 6/5). Seventeen out of 18 benefited from the fusion-based prediction as compared to the ECG-only-based prediction, the traditional prospective gating method. Only one patient whose SCG was compromised by noise was more suitable for ECG-only-based prediction. On average, our fused ECG-SCG-based method improves cardiac quiescence prediction by 47% over ECG-only-based method; with both compared against the gold standard, B-mode echocardiography. Fusion-based prediction is also more resistant to heart rate variability than ECG-only- or SCG-only-based prediction. To assess the clinical value, the diagnostic quality of the CCTA reconstructed volumes from the quiescence derived from ECG-, SCG- and fusion-based predictions were graded by a board-certified radiologist using a Likert response format. Grading results indicated the fusion-based prediction improved diagnostic quality. ECG may be a sub-optimal modality for quiescence prediction and can be enhanced by the multimodal framework. The combination of ECG and SCG signals for quiescence prediction bears promise for a more personalized and reliable approach than ECG-only-based method to predict cardiac quiescence for prospective CCTA gating.

Modeling Intracochlear Magnetic Stimulation: A Finite-Element Analysis.

This study models induced electric fields, and their gradient, produced by pulsatile current stimulation of submillimeter inductors for cochlear implantation. Using finite-element analysis, the lower chamber of the cochlea, scala tympani, is modeled as a cylindrical structure filled with perilymph bounded by tissue, bone, and cochlear neural elements. Single inductors as well as an array of inductors are modeled. The coil strength (~100 nH) and excitation parameters (peak current of 1-5 A, voltages of 16-20 V) are based on a formative feasibility study conducted by our group. In that study, intracochlear micromagnetic stimulation achieved auditory activation as measured through the auditory brainstem response in a feline model. With respect to the finite element simulations, axial symmetry of the inductor geometry is exploited to improve computation time. It is verified that the inductor coil orientation greatly affects the strength of the induced electric field and thereby the ability to affect the transmembrane potential of nearby neural elements. Furthermore, upon comparing an array of micro-inductors with a typical multi-site electrode array, magnetically excited arrays retain greater focus in terms of the gradient of induced electric fields. Once combined with further in vivo analysis, this modeling study may enable further exploration of the mechanism of magnetically induced, and focused neural stimulation.

Echocardiography as an indication of continuous-time cardiac quiescence.

Cardiac computed tomography (CT) angiography using prospective gating requires that data be acquired during intervals of minimal cardiac motion to obtain diagnostic images of the coronary vessels free of motion artifacts. This work is intended to assess B-mode echocardiography as a continuous-time indication of these quiescent periods to determine if echocardiography can be used as a cost-efficient, non-ionizing modality to develop new prospective gating techniques for cardiac CT. These new prospective gating approaches will not be based on echocardiography itself but on CT-compatible modalities derived from the mechanics of the heart (e.g. seismocardiography and impedance cardiography), unlike the current standard electrocardiogram. To this end, echocardiography and retrospectively-gated CT data were obtained from ten patients with varied cardiac conditions. CT reconstructions were made throughout the cardiac cycle. Motion of the interventricular septum (IVS) was calculated from both echocardiography and CT reconstructions using correlation-based, deviation techniques. The IVS was chosen because it (1) is visible in echocardiography images, whereas the coronary vessels generally are not, and (2) has been shown to be a suitable indicator of cardiac quiescence. Quiescent phases were calculated as the minima of IVS motion and CT volumes were reconstructed for these phases. The diagnostic quality of the CT reconstructions from phases calculated from echocardiography and CT data was graded on a four-point Likert scale by a board-certified radiologist fellowship-trained in cardiothoracic radiology. Using a Wilcoxon signed-rank test, no significant difference in the diagnostic quality of the coronary vessels was found between CT volumes reconstructed from echocardiography- and CT-selected phases. Additionally, there was a correlation of 0.956 between the echocardiography- and CT-selected phases. This initial work suggests that B-mode echocardiography can be used as a tool to develop CT-compatible gating techniques based on modalities derived from cardiac mechanics rather than relying on the ECG alone.

Highly Flexible Silicone Coated Neural Array for Intracochlear Electrical Stimulation.

We present an effective method for tailoring the flexibility of a commercial thin-film polymer electrode array for intracochlear electrical stimulation. Using a pneumatically driven dispensing system, an average 232 ± 64 µm (mean ± SD) thickness layer of silicone adhesive coating was applied to stiffen the underside of polyimide multisite arrays. Additional silicone was applied to the tip to protect neural tissue during insertion and along the array to improve surgical handling. Each array supported 20 platinum sites (180 µm dia., 250 µm pitch), spanning nearly 28 mm in length and 400 µm in width. We report an average intracochlear stimulating current threshold of 170 ± 93 µA to evoke an auditory brainstem response in 7 acutely deafened felines. A total of 10 arrays were each inserted through a round window approach into the cochlea's basal turn of eight felines with one delamination occurring upon insertion (preliminary results of the in vivo data presented at the 48th Annual Meeting American Neurotology Society, Orlando, FL, April 2013, and reported in Van Beek-King 2014). Using microcomputed tomography imaging (50 µm resolution), distances ranging from 100 to 565 µm from the cochlea's central modiolus were measured. Our method combines the utility of readily available commercial devices with a straightforward postprocessing step on the order of 24 hours.

Increased frequency of chromosome translocations in airline pilots with long-term flying experience.

BACKGROUND: Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. METHODS: We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. RESULTS: There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). CONCLUSIONS: Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.

Discrimination of sonographically detected breast masses using frequency shift color Doppler imaging in combination with age and gray scale criteria.

Frequency shift color Doppler imaging was assessed in conjunction with patient age and gray scale (GS) features for discriminating benign from malignant breast masses. Thirty-eight women with sonographically detected masses scheduled for biopsy were evaluated using a 6- to 13-MHz scan head, and the masses were delineated in ultrasonographic image volumes. Vascularity in and around each mass was quantified using speed-weighted pixel density (SWD). Gray scale features were ranked visually on a linear scale. Combinations of indices were compared with histologic findings (18 benign and 20 malignant). Receiver operating characteristic analysis ranked performance in decreasing order from the SWD-Age-GS index, to SWD-GS, SWD-Age, Age-GS, GS criteria, SWD, and Age. At 100% sensitivity, SWD-Age-GS, SWD-GS, and SWD-Age discriminated benign from malignant masses with specificities of 94%, 89%, and 72%, respectively. These results indicate significant improvement in ultrasonographic discrimination of sonographically detected breast masses by combining the vascularity measure SWD with age and GS criteria.

Fibrodysplasia ossificans circumscripta of the masseter muscle.

Fibrodysplasia ossificans circumscripta (FOC) is a lesion characterized by localized calcification of the investing fascia of skeletal muscle. It is often related to repeated trauma and was formerly known as traumatic myositis ossificans. Surgical procedures involving muscles are also believed to be a factor in the origin of the lesion. When FOC develops in the muscles of mastication it can lead to severe trismus. A case is reported of FOC in the left masseter muscle of a 44-year-old man who presented with marked limitation of opening. It was believed that previous fractures of the left maxilla and mandible and/or the subsequent surgical treatments were responsible for the onset of FOC. The radiographic and microscopic features of FOC are discussed in relation to recent theories on the etiology, pathogenesis, and treatment of the lesion.