Linkage analysis of longitudinal data

BACKGROUND: We propose a statistical model for linkage analysis of the longitudinal data. The proposed model is a mixed model based on the new Haseman and Elston model and allows several random effects. Specifically, the proposed model includes a random effect for correlation among sib pairs having one sibling in common, and one for the correlation among siblings from the same parents. RESULTS: The proposed model was applied to the analysis of the Genetic Analysis Workshop 13 simulated data set for a quantitative trait of the systolic blood pressure. A simple independence model and two kinds of random effects models yielded good power for detecting linkage for these data sets, while the random effects models performed slightly better than the independence model. Both random effects models showed similar performance. CONCLUSIONS: The proposed models seem not only quite useful in detecting linkage with the longitudinal data for the trait but also quite flexible. They can handle a wide class of correlation structures. Models with a more general class of covariance structure are desirable

Optimal set of grid size and angular increment for practical dose calculation using the dynamic conformal arc technique: a systematic evaluation of the dosimetric effects in lung stereotactic body radiation therapy

Purpose To recommend the optimal plan parameter set of grid size and angular increment for dose calculations in treatment planning for lung stereotactic body radiation therapy (SBRT) using dynamic conformal arc therapy (DCAT) considering both accuracy and computational efficiency. Materials and methods Dose variations with varying grid sizes (2, 3, and 4 mm) and angular increments (2°, 4°, 6°, and 10°) were analyzed in a thorax phantom for 3 spherical target volumes and in 9 patient cases. A 2-mm grid size and 2° angular increment are assumed sufficient to serve as reference values. The dosimetric effect was evaluated using dose–volume histograms, monitor units (MUs), and dose to organs at risk (OARs) for a definite volume corresponding to the dose–volume constraint in lung SBRT. The times required for dose calculations using each parameter set were compared for clinical practicality. Results Larger grid sizes caused a dose increase to the structures and required higher MUs to achieve the target coverage. The discrete beam arrangements at each angular increment led to over- and under-estimated OARs doses due to the undulating dose distribution. When a 2° angular increment was used in both studies, a 4-mm grid size changed the dose variation by up to 3–4% (50 cGy) for the heart and the spinal cord, while a 3-mm grid size produced a dose difference of \u3c1% (12 cGy) in all tested OARs. When a 3-mm grid size was employed, angular increments of 6° and 10° caused maximum dose variations of 3% (23 cGy) and 10% (61 cGy) in the spinal cord, respectively, while a 4° increment resulted in a dose difference of \u3c1% (8 cGy) in all cases except for that of one patient. The 3-mm grid size and 4° angular increment enabled a 78% savings in computation time without making any critical sacrifices to dose accuracy. Conclusions A parameter set with a 3-mm grid size and a 4° angular increment is found to be appropriate for predicting patient dose distributions with a dose difference below 1% while reducing the computation time by more than half for lung SBRT using DCAT

Strong Contrast Stagnation of Unilateral Vertebral Artery on Three-Dimensional Black Blood-Enhanced MRI Predicts Acute Medulla Infarction

Purpose This study aimed to evaluate angiographic and contrast enhancement (CE) patterns on three-dimensional (3D) black blood (BB) contrast-enhanced MRI in patients with acute medulla infarction. Materials and Methods From January 2020 to August 2021, we retrospectively analyzed stroke 3D BB contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) findings of patients visiting the emergency room for symptom evaluation of acute medulla infarction. In total, 28 patients with acute medulla infarction were enrolled in this study. Four types of 3D BB contrast-enhanced MRI and MRA were classified as follows: 1=unilateral contrast-enhanced vertebral artery (VA)+no visualization of VA on MRA; 2=unilateral enhanced VA+hypoplastic VA; 3=no enhanced VA+unilateral complete occlusion of VA; 4=no enhanced VA+normal VA (including hypoplasia) on MRA. Results Of the 28 patients with acute medulla infarction, 7 (25.0%) showed delayed positive findings after 24 hours on diffusion-weighted imaging (DWI). Of these patients, 19 (67.9%) showed CE of the unilateral VA on 3D BB contrast-enhanced MRI (type 1 and 2). Of the 19 patients with CE of VA on 3D BB contrast-enhanced MRI, 18 showed no visualization of enhanced VA on MRA (type 1), and 1 showed hypoplastic VA. Of the 7 patients with delayed positive findings on DWI, 5 showed CE of the unilateral VA and no visualization of the enhanced VA on MRA (type 1). Symptom onset to door time or initial MR check time was significantly shorter in the groups with delayed positive findings on DWI (P<0.05). Conclusion Unilateral CE on 3D BB contrast-enhanced MRI and no visualization of the VA on MRA are related to the recent occlusion of the distal VA. These findings suggest that the recent occlusion of the distal VA is related to acute medulla infarction, including delayed visualization on DWI

miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human mesenchymal stem cells

AbstractHuman mesenchymal stem cells (hMSCs) have self-renewal and differentiation capabilities but the regulatory mechanisms of MSC fate determination remain poorly understood. Here, we aimed to identify microRNAs enriched in hMSCs that modulate differentiation commitments. Microarray analysis revealed that miR-140-5p is commonly enriched in undifferentiated hMSCs from various tissue sources. Moreover, bioinformatic analysis and luciferase reporter assay validated that miR-140-5p directly represses bone morphogenic protein 2 (BMP2). Furthermore, blocking miR-140-5p in hMSCs increased the expression of BMP signaling components and critical regulators of osteogenic differentiation. We propose that miR-140-5p functionally inhibits osteogenic lineage commitment in undifferentiated hMSCs

The Usefulness of Maximum Standardized Uptake Value at the Delayed Phase of Tc-99m sestamibi single-photon emission computed tomography/computed tomography for Identification of Parathyroid Adenoma and Hyperplasia

Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism. Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 +/- 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells. SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 +/- 6.68, 7.90 +/- 5.49, and 7.01 +/- 2.62 at 10min (early phase), decreasing to 7.46 +/- 5.66, 4.65 +/- 3.14, and 2.21 +/- 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P &lt; .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of oxyphil cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant oxyphil cells (rho = 0.418,P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions. SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.Y