Three-dimensional Ultrasound Measurements of Carotid Atherosclerosis in Vulnerable Patient Populations

Atherosclerosis is a progressive disease that leads to plaque development and is associated with cardiovascular events such as myocardial infarction and stroke. Several biomarkers have been established as surrogates of plaque development yet none can provide direct, noninvasive, rapid measurements of atherosclerotic disease. Three-dimensional Ultrasound (3DUS) image acquisition is safe, inexpensive and fast, however 3DUS image measurements are limited due to time consuming manual image analyses. In addition, the true clinical meaning of 3DUS carotid imaging measurements has not yet been established. A semi-automated approach for the estimation of 3DUS Total Plaque Volume (TPV) was developed with similar variability and high agreement with manual measurements. 3DUS measurements such as Vessel Wall Volume (VWV) and TPV were shown to have similar associations of plaque and Intima-media Thickness (IMT) with age in males however this relationship did not exist in females. 3DUS measurements of carotid atherosclerosis can provide a more sensitive estimation of disease burden in vulnerable patient populations than traditional measures

A VIRTUAL CRANKSHAFT THIGH MODEL TO ESTIMATE TIBIAL-FEMORAL TRANSVERSE PLANE KINEMATICS

Sports injuries often require a thorough evaluation of the knee that includes transverse plane measurements, which are difficult to measure accurately using motion capture. We have developed a method to estimate thigh position modelling the lower limb as a modified slider-crank mechanism. Our model does not rely on cutaneous thigh markers; its motion is defined by a functionally determined hip joint center and constrained distally to the tibial plateau. Motion capture was used to acquire normal gait and countermovement jump data from three unimpaired subjects. The transverse plane translations and rotation along with frontal plane rotation estimated by our model were shown to be reflective of those reported in literature. Our slider-crank model of the pelvis-femur-tibia complex has been demonstrated to perform well in both low and high impact motions

Coiling Instability of Multilamellar Membrane Tubes with Anchored Polymers

We study experimentally a coiling instability of cylindrical multilamellar stacks of phospholipid membranes, induced by polymers with hydrophobic anchors grafted along their hydrophilic backbone. Our system is unique in that coils form in the absence of both twist and adhesion. We interpret our experimental results in terms of a model in which local membrane curvature and polymer concentration are coupled. The model predicts the occurrence of maximally tight coils above a threshold polymer occupancy. A proper comparison between the model and experiment involved imaging of projections from simulated coiled tubes with maximal curvature and complicated torsions.Comment: 11 pages + 7 GIF figures + 10 JPEG figure

Monoallelic NTHL1 Loss-of-Function Variants and Risk of Polyposis and Colorectal Cancer

Contains fulltext : 228713.pdf (Publisher’s version ) (Open Access

Association between molecular subtypes of colorectal cancer and patient survival

BACKGROUND and AIMS: Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival. METHODS: Participants in the population-based Seattle Colon Cancer Family Registry were diagnosed with invasive CRC from 1998 through 2007 in western Washington State (N = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 participants and classified into 5 subtypes based on combinations of tumor markers: type 1 (microsatellite instability [MSI]-high, CpG island methylator phenotype [CIMP] -positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMP-positive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS). Multiple imputation was used to impute tumor markers for those missing data on 1-3 markers. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of subtypes with disease-specific and overall mortality, adjusting for age, sex, body mass, diagnosis year, and smoking history. RESULTS: Compared with participants with type 4 tumors (the most predominant), participants with type 2 tumors had the highest disease-specific mortality (HR = 2.20, 95% CI: 1.47-3.31); subjects with type 3 tumors also had higher disease-specific mortality (HR = 1.32, 95% CI: 1.07-1.63). Subjects with type 5 tumors had the lowest disease-specific mortality (HR = 0.30, 95% CI: 0.14-0.66). Associations with overall mortality were similar to those with disease-specific mortality. CONCLUSIONS: Based on a large, population-based study, CRC subtypes, defined by proposed etiologic pathways, are associated with marked differences in survival. These findings indicate the clinical importance of studies into the molecular heterogeneity of CRC

One, two and three-dimensional ultrasound measurements of carotid atherosclerosis before and after cardiac rehabilitation: preliminary results of a randomized controlled trial.

BACKGROUND: It is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR. METHODS: Carotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed consent to participate in this randomized controlled trial. We maintained blinding for this ongoing study by representing treatment and control groups as A or B, although we did not identify which of A or B was treatment or control. Carotid IMT, TPA, TPV and VWV were measured before and after CCR as were changes in body mass index (BMI), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP). RESULTS: There were no significant differences in US measurements or risk factors between groups A and B. There was no significant change in carotid ultrasound measurements for group A (IMT, p = .728; TPA, p = .629; TPV, p = .674; VWV, p = .507) or B (IMT, p = .054; TPA, p = .567; TPV, p = .773; VWV, p = .431) at the end of CCR. There were significant but weak-to-moderate correlations between IMT and VWV (r = 0.25, p = .01), IMT and TPV (r = 0.21, p = .01), TPV and TPA (r = 0.60, p \u3c .0001) and VWV and TPV (r = 0.22, p = .02). Subjects with improved TC/HDL ratios showed improved carotid VWV although, this was not statistically significant. CONCLUSION: In this preliminary evaluation, there were no significant differences in carotid US measurements in the control or CCR group; a larger sample size and/or longer duration is required to detect significant changes in US or other risk factor measurements

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Cholecystectomy and the risk of colorectal cancer by tumor mismatch repair deficiency status

Gallbladder diseases and cholecystectomy may play a role in the development of colorectal cancer (CRC). Our aim was to investigate the association between cholecystectomy and CRC risk overall and by sex, family history, anatomical location, and tumor mismatch repair (MMR) status

Widespread platinum anomaly documented at theYounger Dryas onset in North American sedimentary sequences

Previously, a large platinum (Pt) anomaly was reported in the Greenland ice sheet at the Younger Dryas boundary (YDB) (12,800 Cal B.P.). In order to evaluate its geographic extent, fire-assay and inductively coupled plasma mass spectrometry (FA and ICP-MS) elemental analyses were performed on 11 widely separated archaeological bulk sedimentary sequences. We document discovery of a distinct Pt anomaly spread widely across North America and dating to the Younger Dryas (YD) onset. The apparent synchroneity of this widespread YDB Pt anomaly is consistent with Greenland Ice Sheet Project 2 (GISP2) data that indicated atmospheric input of platinum-rich dust. We expect the Pt anomaly to serve as a widely-distributed time marker horizon (datum) for identification and correlation of the onset of the YD climatic episode at 12,800 Cal B.P. This Pt datum will facilitate the dating and correlating of archaeological, paleontological, and paleoenvironmental data between sequences, especially those with limited age control