Right bundle branch block and risk of cardiovascular mortality: the Ibaraki Prefectural Health Study.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards' models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06-1.38). The increased risk of cardiovascular mortality was particularly evident in women aged < 65 years (HR 2.00; 95% CI 1.34-2.98) and men aged ≥ 65 years (HR 1.28; 95% CI 1.06-1.55). CRBBB is associated with an increased risk of cardiovascular mortality in women aged < 65 years and men aged ≥ 65 years. Clinicians should be aware of the presence of CRBBB in young women and elderly men, even if they exhibit no symptoms.

Use of Mixer Torque Rheometer to Clarify the Relationship between the Kneading States of Wet Mass and the Dissolution of Final Product in High Shear Granulation.

The properties of wet mass, which indicate the progress of high shear granulation processes, usually have an effect on final product properties, such as tablet dissolution. The mixer torque rheometer (MTR) is a useful tool for quantitatively measuring the 'kneading state' of wet mass and detecting differences in granules. However, there have been no studies of the relationship between the MTR torque and the final product properties to date. In this study, we measured the MTR torque of wet granules at different kneading states, which were prepared by changing the granulation conditions. We then evaluated the relationship between the MTR torque and the dissolution rate of the final product properties. The amperage of the high shear granulator is usually monitored during granulation, but we could not detect a difference in the kneading state through the amperage. However, using MTR torque we were able to quantify the difference of the wet mass. Moreover, MTR torque showed a high correlation with dissolution, compared with the correlations with other intermediate properties, such as granules particle size and tablet hardness. These other properties are affected by following processes and are not properties that directly relate to the kneading state. Thus, MTR torque is a property of wet mass after granulation, and it can be used to directly evaluate differences of the kneading state, and as a result, dissolution. These results indicate the importance of controlling the kneading state, i.e., the progress of granulation, and the utility of MTR for detecting differences in wet mass.

[Estimation of the Average Glandular Dose Using the Mammary Gland Image Analysis in Mammography].

Currently, the glandular dose is evaluated quantitatively on the basis of the measured data using phantom, and not in a dose based on the mammary gland structure of an individual patient. However, mammary gland structures of the patients are different from each other and mammary gland dose of an individual patient cannot be obtained by the existing methods. In this study, we present an automated estimation method of mammary gland dose by means of mammary structure which is measured automatically using mammogram. In this method, mammary gland structure is extracted by Gabor filter; mammary region is segmented by the automated thresholding. For the evaluation, mammograms of 100 patients diagnosed with category 1 were collected. Using these mammograms we compared the mammary gland ratio measured by proposed method and visual evaluation. As a result, 78% of the total cases were matched. Furthermore, the mammary gland ratio and average glandular dose among the patients with same breast thickness was matched well. These results show that the proposed method may be useful for the estimation of average glandular dose for the individual patients.

Preliminary study on the automated skull fracture detection in CT images using black-hat transform.

Linear skull fracture, following head trauma, may reach major blood vessels, such as the middle meningeal artery or sinus venosus, and may cause epidural hematoma. However, hematoma is likely to be missed in the initial interpretation because it spreads only gradually. In addition, the fracture lines that run along the scan slice plane are often missed during initial interpretation. In this study, we develop a novel method for automated detection of the linear skull fracture using head computed tomography (CT) images and conduct a basic evaluation using digital phantom and head phantom that enclose genuine human bones. In the proposed method, the bone region is first extracted using morphological processing of the head CT images. Then, the cranial vault is determined from the CT scout view image. The skull has low-density cancellous bone between the hard two-layer high-density compact bones. Because the fracture lines of compact bones are more clearly recognized as compared to cancellous bones, the bone surface is then extracted by performing three-dimensional (3D) Laplacian filtering. Finally, linear structures are extracted by applying the black-hat transform to the bone surface image. In the experiments, we evaluated the proposed method using digital phantom and CT images of the head phantom. From the experiments using digital phantom, we were able to detect a crack line with a width of 0.35 mm. In the experiments using head phantom, we were able to clearly detect the crack lines in the phantom. These results indicate that our proposed method will be useful for the automated detection of skull fracture in CT images.

Patient investigation of average glandular dose and incident air kerma for digital mammography.

Our aim in this study was to investigate the incident air kerma (IAK) and average glandular dose (AGD) for polymethylmethacrylate (PMMA) phantoms and patient breasts for each thickness by use of digital mammography units, and to determine the correlation between phantom and patient measurements. An additional aim was to calculate the numerical value of the diagnostic reference level (DRL) for digital mammography in Japan based on the AGD from patient measurements. Patient-based IAK and AGD values were calculated for 300 patients who underwent mammographic examinations at three institutions. On examination of a 40-mm PMMA phantom, the IAK and the AGD were 7.89 and 1.84 mGy, respectively. The mean patient breast thickness was 37.6 mm, and the mean IAK and the AGD calculated from actual patient data for breast thicknesses between 40 mm and 50 mm were 8.91 and 2.08 mGy, respectively. Approximately 20 % of the 300 patients had IAK >10 mGy. The distributions of patient-based IAK and AGD values were higher than the IAK and AGD values for the PMMA phantom. The patient dose with use of the PMMA phantom can be underestimated. The DRL was calculated from patient-based AGDs of the regular breast thickness as 2.0 mGy in Japan.

Influence of binder droplet dimension on granulation rate during fluidized bed granulation.

Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.

Evaluation of models for predicting spray mist diameter for scaling-up of the fluidized bed granulation process.

We evaluated models for predicting spray mist diameter suitable for scaling-up the fluidized bed granulation process. By precise selection of experimental conditions, we were able to identify a suitable prediction model that considers changes in binder solution, nozzle dimension, and spray conditions. We used hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or polyvinylpyrrolidone (PVP) binder solutions, which are commonly employed by the pharmaceutical industry. Nozzle dimension and spray conditions for oral dosing were carefully selected to reflect manufacturing and small (1/10) scale process conditions. We were able to demonstrate that the prediction model proposed by Mulhem optimally estimated spray mist diameter when each coefficient was modified. Moreover, we developed a simple scale-up rule to produce the same spray mist diameter at different process scales. We confirmed that the Rosin-Rammler distribution could be applied to this process, and that its distribution coefficient was 1.43-1.72 regardless of binder solution, spray condition, or nozzle dimension.

[Dose evaluation in mammography for Japanese breast thickness].

Accuracy control of mammography equipment involves more than just equipment management; the proportions of the mammary glands used to obtain appropriate images is also important, as is control of the glandular X-ray dose in accordance with thickness. Methods for evaluating glandular dose include the ACR, EUREF, and IAEA protocols. The aim of this study was to elucidate the differences between the various protocols and to suggest a dose evaluation method suited to Japanese breast thickness. An ionization chamber dosimeter was used for dose measurement, with a 156 phantom used as a breast phantom for the ACR and a PMMA phantom used for the EUREF and IAEA. There were no major differences in the protocols. The AGDs in the breast phantoms recommended HVLs for each protocol but were 25-30% higher in the EUREF and IAEA compared with the ACR, owing to the different breast thicknesses in each case. The IAEA should be regarded as the basic method for implementing optimum accuracy control in Japan, and a 35-mm PMMA should be used to correspond most closely to Japanese breast thickness.

Application of principal component analysis enables to effectively find important physical variables for optimization of fluid bed granulator conditions.

Principal component analysis was applied to effectively optimize the operational conditions of a fluidized bed granulator for preparing granules with excellent compaction and tablet physical properties. The crucial variables that affect the properties of the granules, their compactability and the resulting tablet properties were determined through analysis of a series of granulation and tabletting experiments. Granulation was performed while the flow rate and concentration of the binder were changed as independent operational variables, according to a two-factor central composite design. Thirteen physicochemical properties of granules and tablets were examined: powder properties (particle size, size distribution width, Carr's index, Hausner ratio and aspect ratio), compactability properties (pressure transmission ratio, die wall force and ejection force) and tablet properties (tensile strength, friability, disintegration time, weight variation and drug content uniformity). Principal component analysis showed that the pressure transmission ratio, die wall force and Carr's index were the most important variables in granule preparation. Multiple regression analysis also confirmed these results. Furthermore, optimized operational conditions obtained from the multiple regression analysis enabled the production of granules with desirable properties for tabletting. This study presents the first use of principle component analysis for identifying and successfully predicting the most important variables in the process of granulation and tabletting.

Modulation of olfactory learning in young rats through intrabulbar GABA(B) receptors.

After training with an odour paired with foot shock on postnatal day 11, rat pups show an aversion to the odour in testing on postnatal day 12. The mechanisms underlying this aversive olfactory learning involve disinhibition of mitral/tufted cells in the olfactory bulb by the somatosensory stimulation-induced activation of centrifugal noradrenergic fibres originating in the locus coeruleus. The activity of mitral/tufted cells is regulated through gamma-aminobutyric acidA (GABA(A)) receptors in the external plexiform layer and GABA(B) receptors in the glomerular layer. We have previously presented that aversive olfactory learning in young rats is modulated through GABA(A) receptors in the olfactory bulb. In the present study we examined the consequence of manipulating GABA(B) receptors in the olfactory bulb during training. Baclofen, a GABA(B) receptor agonist when infused into the olfactory bulb during the pairing of an odour with foot shock, prevented aversive olfactory learning in a dose-dependent manner. Infusion of saclofen, a GABA(B) receptor antagonist, during training with a citral odour in the absence of foot shock produced aversive responses not only to the odour, but also to strange odours (benzaldehyde and vanillin) not previously presented. Such olfactory aversions were observed even if saclofen was infused without odour exposure. These results suggest that olfactory learning in young rats is modulated through GABA(B) receptors in the olfactory bulb.